How to Write a Conclusion for Research Papers (with Examples)

How to Write a Conclusion for Research Papers (with Examples)

The conclusion of a research paper is a crucial section that plays a significant role in the overall impact and effectiveness of your research paper. However, this is also the section that typically receives less attention compared to the introduction and the body of the paper. The conclusion serves to provide a concise summary of the key findings, their significance, their implications, and a sense of closure to the study. Discussing how can the findings be applied in real-world scenarios or inform policy, practice, or decision-making is especially valuable to practitioners and policymakers. The research paper conclusion also provides researchers with clear insights and valuable information for their own work, which they can then build on and contribute to the advancement of knowledge in the field.

The research paper conclusion should explain the significance of your findings within the broader context of your field. It restates how your results contribute to the existing body of knowledge and whether they confirm or challenge existing theories or hypotheses. Also, by identifying unanswered questions or areas requiring further investigation, your awareness of the broader research landscape can be demonstrated.

Remember to tailor the research paper conclusion to the specific needs and interests of your intended audience, which may include researchers, practitioners, policymakers, or a combination of these.

Table of Contents

What is a conclusion in a research paper, summarizing conclusion, editorial conclusion, externalizing conclusion, importance of a good research paper conclusion, how to write a conclusion for your research paper, research paper conclusion examples, frequently asked questions.

A conclusion in a research paper is the final section where you summarize and wrap up your research, presenting the key findings and insights derived from your study. The research paper conclusion is not the place to introduce new information or data that was not discussed in the main body of the paper. When working on how to conclude a research paper, remember to stick to summarizing and interpreting existing content. The research paper conclusion serves the following purposes: 1

  • Warn readers of the possible consequences of not attending to the problem.
  • Recommend specific course(s) of action.
  • Restate key ideas to drive home the ultimate point of your research paper.
  • Provide a “take-home” message that you want the readers to remember about your study.

research article conclusion

Types of conclusions for research papers

In research papers, the conclusion provides closure to the reader. The type of research paper conclusion you choose depends on the nature of your study, your goals, and your target audience. I provide you with three common types of conclusions:

A summarizing conclusion is the most common type of conclusion in research papers. It involves summarizing the main points, reiterating the research question, and restating the significance of the findings. This common type of research paper conclusion is used across different disciplines.

An editorial conclusion is less common but can be used in research papers that are focused on proposing or advocating for a particular viewpoint or policy. It involves presenting a strong editorial or opinion based on the research findings and offering recommendations or calls to action.

An externalizing conclusion is a type of conclusion that extends the research beyond the scope of the paper by suggesting potential future research directions or discussing the broader implications of the findings. This type of conclusion is often used in more theoretical or exploratory research papers.

The conclusion in a research paper serves several important purposes:

  • Offers Implications and Recommendations : Your research paper conclusion is an excellent place to discuss the broader implications of your research and suggest potential areas for further study. It’s also an opportunity to offer practical recommendations based on your findings.
  • Provides Closure : A good research paper conclusion provides a sense of closure to your paper. It should leave the reader with a feeling that they have reached the end of a well-structured and thought-provoking research project.
  • Leaves a Lasting Impression : Writing a well-crafted research paper conclusion leaves a lasting impression on your readers. It’s your final opportunity to leave them with a new idea, a call to action, or a memorable quote.

research article conclusion

Writing a strong conclusion for your research paper is essential to leave a lasting impression on your readers. Here’s a step-by-step process to help you create and know what to put in the conclusion of a research paper: 2

  • Research Statement : Begin your research paper conclusion by restating your research statement. This reminds the reader of the main point you’ve been trying to prove throughout your paper. Keep it concise and clear.
  • Key Points : Summarize the main arguments and key points you’ve made in your paper. Avoid introducing new information in the research paper conclusion. Instead, provide a concise overview of what you’ve discussed in the body of your paper.
  • Address the Research Questions : If your research paper is based on specific research questions or hypotheses, briefly address whether you’ve answered them or achieved your research goals. Discuss the significance of your findings in this context.
  • Significance : Highlight the importance of your research and its relevance in the broader context. Explain why your findings matter and how they contribute to the existing knowledge in your field.
  • Implications : Explore the practical or theoretical implications of your research. How might your findings impact future research, policy, or real-world applications? Consider the “so what?” question.
  • Future Research : Offer suggestions for future research in your area. What questions or aspects remain unanswered or warrant further investigation? This shows that your work opens the door for future exploration.
  • Closing Thought : Conclude your research paper conclusion with a thought-provoking or memorable statement. This can leave a lasting impression on your readers and wrap up your paper effectively. Avoid introducing new information or arguments here.
  • Proofread and Revise : Carefully proofread your conclusion for grammar, spelling, and clarity. Ensure that your ideas flow smoothly and that your conclusion is coherent and well-structured.

Remember that a well-crafted research paper conclusion is a reflection of the strength of your research and your ability to communicate its significance effectively. It should leave a lasting impression on your readers and tie together all the threads of your paper. Now you know how to start the conclusion of a research paper and what elements to include to make it impactful, let’s look at a research paper conclusion sample.

research article conclusion

The research paper conclusion is a crucial part of your paper as it provides the final opportunity to leave a strong impression on your readers. In the research paper conclusion, summarize the main points of your research paper by restating your research statement, highlighting the most important findings, addressing the research questions or objectives, explaining the broader context of the study, discussing the significance of your findings, providing recommendations if applicable, and emphasizing the takeaway message. The main purpose of the conclusion is to remind the reader of the main point or argument of your paper and to provide a clear and concise summary of the key findings and their implications. All these elements should feature on your list of what to put in the conclusion of a research paper to create a strong final statement for your work.

A strong conclusion is a critical component of a research paper, as it provides an opportunity to wrap up your arguments, reiterate your main points, and leave a lasting impression on your readers. Here are the key elements of a strong research paper conclusion: 1. Conciseness : A research paper conclusion should be concise and to the point. It should not introduce new information or ideas that were not discussed in the body of the paper. 2. Summarization : The research paper conclusion should be comprehensive enough to give the reader a clear understanding of the research’s main contributions. 3 . Relevance : Ensure that the information included in the research paper conclusion is directly relevant to the research paper’s main topic and objectives; avoid unnecessary details. 4 . Connection to the Introduction : A well-structured research paper conclusion often revisits the key points made in the introduction and shows how the research has addressed the initial questions or objectives. 5. Emphasis : Highlight the significance and implications of your research. Why is your study important? What are the broader implications or applications of your findings? 6 . Call to Action : Include a call to action or a recommendation for future research or action based on your findings.

The length of a research paper conclusion can vary depending on several factors, including the overall length of the paper, the complexity of the research, and the specific journal requirements. While there is no strict rule for the length of a conclusion, but it’s generally advisable to keep it relatively short. A typical research paper conclusion might be around 5-10% of the paper’s total length. For example, if your paper is 10 pages long, the conclusion might be roughly half a page to one page in length.

In general, you do not need to include citations in the research paper conclusion. Citations are typically reserved for the body of the paper to support your arguments and provide evidence for your claims. However, there may be some exceptions to this rule: 1. If you are drawing a direct quote or paraphrasing a specific source in your research paper conclusion, you should include a citation to give proper credit to the original author. 2. If your conclusion refers to or discusses specific research, data, or sources that are crucial to the overall argument, citations can be included to reinforce your conclusion’s validity.

The conclusion of a research paper serves several important purposes: 1. Summarize the Key Points 2. Reinforce the Main Argument 3. Provide Closure 4. Offer Insights or Implications 5. Engage the Reader. 6. Reflect on Limitations

Remember that the primary purpose of the research paper conclusion is to leave a lasting impression on the reader, reinforcing the key points and providing closure to your research. It’s often the last part of the paper that the reader will see, so it should be strong and well-crafted.

  • Makar, G., Foltz, C., Lendner, M., & Vaccaro, A. R. (2018). How to write effective discussion and conclusion sections. Clinical spine surgery, 31(8), 345-346.
  • Bunton, D. (2005). The structure of PhD conclusion chapters.  Journal of English for academic purposes ,  4 (3), 207-224.

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The conclusion is intended to help the reader understand why your research should matter to them after they have finished reading the paper. A conclusion is not merely a summary of the main topics covered or a re-statement of your research problem, but a synthesis of key points and, if applicable, where you recommend new areas for future research. For most college-level research papers, one or two well-developed paragraphs is sufficient for a conclusion, although in some cases, more paragraphs may be required in summarizing key findings and their significance.

Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University.

Importance of a Good Conclusion

A well-written conclusion provides you with important opportunities to demonstrate to the reader your understanding of the research problem. These include:

  • Presenting the last word on the issues you raised in your paper . Just as the introduction gives a first impression to your reader, the conclusion offers a chance to leave a lasting impression. Do this, for example, by highlighting key findings in your analysis that advance new understanding about the research problem, that are unusual or unexpected, or that have important implications applied to practice.
  • Summarizing your thoughts and conveying the larger significance of your study . The conclusion is an opportunity to succinctly re-emphasize  the "So What?" question by placing the study within the context of how your research advances past research about the topic.
  • Identifying how a gap in the literature has been addressed . The conclusion can be where you describe how a previously identified gap in the literature [described in your literature review section] has been filled by your research.
  • Demonstrating the importance of your ideas . Don't be shy. The conclusion offers you the opportunity to elaborate on the impact and significance of your findings. This is particularly important if your study approached examining the research problem from an unusual or innovative perspective.
  • Introducing possible new or expanded ways of thinking about the research problem . This does not refer to introducing new information [which should be avoided], but to offer new insight and creative approaches for framing or contextualizing the research problem based on the results of your study.

Bunton, David. “The Structure of PhD Conclusion Chapters.” Journal of English for Academic Purposes 4 (July 2005): 207–224; Conclusions. The Writing Center. University of North Carolina; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Conclusions. The Writing Lab and The OWL. Purdue University; Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Structure and Writing Style

I.  General Rules

The function of your paper's conclusion is to restate the main argument . It reminds the reader of the strengths of your main argument(s) and reiterates the most important evidence supporting those argument(s). Do this by stating clearly the context, background, and necessity of pursuing the research problem you investigated in relation to an issue, controversy, or a gap found in the literature. Make sure, however, that your conclusion is not simply a repetitive summary of the findings. This reduces the impact of the argument(s) you have developed in your essay.

When writing the conclusion to your paper, follow these general rules:

  • Present your conclusions in clear, simple language. Re-state the purpose of your study, then describe how your findings differ or support those of other studies and why [i.e., what were the unique or new contributions your study made to the overall research about your topic?].
  • Do not simply reiterate your findings or the discussion of your results. Provide a synthesis of arguments presented in the paper to show how these converge to address the research problem and the overall objectives of your study.
  • Indicate opportunities for future research if you haven't already done so in the discussion section of your paper. Highlighting the need for further research provides the reader with evidence that you have an in-depth awareness of the research problem and that further investigations should take place.

Consider the following points to help ensure your conclusion is presented well:

  • If the argument or purpose of your paper is complex, you may need to summarize the argument for your reader.
  • If, prior to your conclusion, you have not yet explained the significance of your findings or if you are proceeding inductively, use the end of your paper to describe your main points and explain their significance.
  • Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction or within a new context that emerges from the data. 

The conclusion also provides a place for you to persuasively and succinctly restate the research problem, given that the reader has now been presented with all the information about the topic . Depending on the discipline you are writing in, the concluding paragraph may contain your reflections on the evidence presented. However, the nature of being introspective about the research you have conducted will depend on the topic and whether your professor wants you to express your observations in this way.

NOTE : If asked to think introspectively about the topics, do not delve into idle speculation. Being introspective means looking within yourself as an author to try and understand an issue more deeply, not to guess at possible outcomes or make up scenarios not supported by the evidence.

II.  Developing a Compelling Conclusion

Although an effective conclusion needs to be clear and succinct, it does not need to be written passively or lack a compelling narrative. Strategies to help you move beyond merely summarizing the key points of your research paper may include any of the following strategies:

  • If your essay deals with a critical, contemporary problem, warn readers of the possible consequences of not attending to the problem proactively.
  • Recommend a specific course or courses of action that, if adopted, could address a specific problem in practice or in the development of new knowledge.
  • Cite a relevant quotation or expert opinion already noted in your paper in order to lend authority and support to the conclusion(s) you have reached [a good place to look is research from your literature review].
  • Explain the consequences of your research in a way that elicits action or demonstrates urgency in seeking change.
  • Restate a key statistic, fact, or visual image to emphasize the most important finding of your paper.
  • If your discipline encourages personal reflection, illustrate your concluding point by drawing from your own life experiences.
  • Return to an anecdote, an example, or a quotation that you presented in your introduction, but add further insight derived from the findings of your study; use your interpretation of results to recast it in new or important ways.
  • Provide a "take-home" message in the form of a succinct, declarative statement that you want the reader to remember about your study.

III. Problems to Avoid

Failure to be concise Your conclusion section should be concise and to the point. Conclusions that are too lengthy often have unnecessary information in them. The conclusion is not the place for details about your methodology or results. Although you should give a summary of what was learned from your research, this summary should be relatively brief, since the emphasis in the conclusion is on the implications, evaluations, insights, and other forms of analysis that you make. Strategies for writing concisely can be found here .

Failure to comment on larger, more significant issues In the introduction, your task was to move from the general [the field of study] to the specific [the research problem]. However, in the conclusion, your task is to move from a specific discussion [your research problem] back to a general discussion [i.e., how your research contributes new understanding or fills an important gap in the literature]. In short, the conclusion is where you should place your research within a larger context [visualize your paper as an hourglass--start with a broad introduction and review of the literature, move to the specific analysis and discussion, conclude with a broad summary of the study's implications and significance].

Failure to reveal problems and negative results Negative aspects of the research process should never be ignored. These are problems, deficiencies, or challenges encountered during your study should be summarized as a way of qualifying your overall conclusions. If you encountered negative or unintended results [i.e., findings that are validated outside the research context in which they were generated], you must report them in the results section and discuss their implications in the discussion section of your paper. In the conclusion, use your summary of the negative results as an opportunity to explain their possible significance and/or how they may form the basis for future research.

Failure to provide a clear summary of what was learned In order to be able to discuss how your research fits within your field of study [and possibly the world at large], you need to summarize briefly and succinctly how it contributes to new knowledge or a new understanding about the research problem. This element of your conclusion may be only a few sentences long.

Failure to match the objectives of your research Often research objectives in the social sciences change while the research is being carried out. This is not a problem unless you forget to go back and refine the original objectives in your introduction. As these changes emerge they must be documented so that they accurately reflect what you were trying to accomplish in your research [not what you thought you might accomplish when you began].

Resist the urge to apologize If you've immersed yourself in studying the research problem, you presumably should know a good deal about it [perhaps even more than your professor!]. Nevertheless, by the time you have finished writing, you may be having some doubts about what you have produced. Repress those doubts! Don't undermine your authority by saying something like, "This is just one approach to examining this problem; there may be other, much better approaches that...." The overall tone of your conclusion should convey confidence to the reader.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Concluding Paragraphs. College Writing Center at Meramec. St. Louis Community College; Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University; Freedman, Leora  and Jerry Plotnick. Introductions and Conclusions. The Lab Report. University College Writing Centre. University of Toronto; Leibensperger, Summer. Draft Your Conclusion. Academic Center, the University of Houston-Victoria, 2003; Make Your Last Words Count. The Writer’s Handbook. Writing Center. University of Wisconsin Madison; Miquel, Fuster-Marquez and Carmen Gregori-Signes. “Chapter Six: ‘Last but Not Least:’ Writing the Conclusion of Your Paper.” In Writing an Applied Linguistics Thesis or Dissertation: A Guide to Presenting Empirical Research . John Bitchener, editor. (Basingstoke,UK: Palgrave Macmillan, 2010), pp. 93-105; Tips for Writing a Good Conclusion. Writing@CSU. Colorado State University; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Writing Conclusions. Writing Tutorial Services, Center for Innovative Teaching and Learning. Indiana University; Writing: Considering Structure and Organization. Institute for Writing Rhetoric. Dartmouth College.

Writing Tip

Don't Belabor the Obvious!

Avoid phrases like "in conclusion...," "in summary...," or "in closing...." These phrases can be useful, even welcome, in oral presentations. But readers can see by the tell-tale section heading and number of pages remaining to read, when an essay is about to end. You'll irritate your readers if you belabor the obvious.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Another Writing Tip

New Insight, Not New Information!

Don't surprise the reader with new information in your conclusion that was never referenced anywhere else in the paper and, as such, the conclusion rarely has citations to sources. If you have new information to present, add it to the discussion or other appropriate section of the paper. Note that, although no actual new information is introduced, the conclusion, along with the discussion section, is where you offer your most "original" contributions in the paper; the conclusion is where you describe the value of your research, demonstrate that you understand the material that you’ve presented, and locate your findings within the larger context of scholarship on the topic, including describing how your research contributes new insights or valuable insight to that scholarship.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Conclusions. The Writing Center. University of North Carolina.

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  • How to Write Discussions and Conclusions

How to Write Discussions and Conclusions

The discussion section contains the results and outcomes of a study. An effective discussion informs readers what can be learned from your experiment and provides context for the results.

What makes an effective discussion?

When you’re ready to write your discussion, you’ve already introduced the purpose of your study and provided an in-depth description of the methodology. The discussion informs readers about the larger implications of your study based on the results. Highlighting these implications while not overstating the findings can be challenging, especially when you’re submitting to a journal that selects articles based on novelty or potential impact. Regardless of what journal you are submitting to, the discussion section always serves the same purpose: concluding what your study results actually mean.

A successful discussion section puts your findings in context. It should include:

  • the results of your research,
  • a discussion of related research, and
  • a comparison between your results and initial hypothesis.

Tip: Not all journals share the same naming conventions.

You can apply the advice in this article to the conclusion, results or discussion sections of your manuscript.

Our Early Career Researcher community tells us that the conclusion is often considered the most difficult aspect of a manuscript to write. To help, this guide provides questions to ask yourself, a basic structure to model your discussion off of and examples from published manuscripts. 

research article conclusion

Questions to ask yourself:

  • Was my hypothesis correct?
  • If my hypothesis is partially correct or entirely different, what can be learned from the results? 
  • How do the conclusions reshape or add onto the existing knowledge in the field? What does previous research say about the topic? 
  • Why are the results important or relevant to your audience? Do they add further evidence to a scientific consensus or disprove prior studies? 
  • How can future research build on these observations? What are the key experiments that must be done? 
  • What is the “take-home” message you want your reader to leave with?

How to structure a discussion

Trying to fit a complete discussion into a single paragraph can add unnecessary stress to the writing process. If possible, you’ll want to give yourself two or three paragraphs to give the reader a comprehensive understanding of your study as a whole. Here’s one way to structure an effective discussion:

research article conclusion

Writing Tips

While the above sections can help you brainstorm and structure your discussion, there are many common mistakes that writers revert to when having difficulties with their paper. Writing a discussion can be a delicate balance between summarizing your results, providing proper context for your research and avoiding introducing new information. Remember that your paper should be both confident and honest about the results! 

What to do

  • Read the journal’s guidelines on the discussion and conclusion sections. If possible, learn about the guidelines before writing the discussion to ensure you’re writing to meet their expectations. 
  • Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. 
  • Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and limitations of the research. 
  • State whether the results prove or disprove your hypothesis. If your hypothesis was disproved, what might be the reasons? 
  • Introduce new or expanded ways to think about the research question. Indicate what next steps can be taken to further pursue any unresolved questions. 
  • If dealing with a contemporary or ongoing problem, such as climate change, discuss possible consequences if the problem is avoided. 
  • Be concise. Adding unnecessary detail can distract from the main findings. 

What not to do


  • Rewrite your abstract. Statements with “we investigated” or “we studied” generally do not belong in the discussion. 
  • Include new arguments or evidence not previously discussed. Necessary information and evidence should be introduced in the main body of the paper. 
  • Apologize. Even if your research contains significant limitations, don’t undermine your authority by including statements that doubt your methodology or execution. 
  • Shy away from speaking on limitations or negative results. Including limitations and negative results will give readers a complete understanding of the presented research. Potential limitations include sources of potential bias, threats to internal or external validity, barriers to implementing an intervention and other issues inherent to the study design. 
  • Overstate the importance of your findings. Making grand statements about how a study will fully resolve large questions can lead readers to doubt the success of the research. 

Snippets of Effective Discussions:

Consumer-based actions to reduce plastic pollution in rivers: A multi-criteria decision analysis approach

Identifying reliable indicators of fitness in polar bears

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Home » Research Paper Conclusion – Writing Guide and Examples

Research Paper Conclusion – Writing Guide and Examples

Table of Contents

Research Paper Conclusion

Research Paper Conclusion


A research paper conclusion is the final section of a research paper that summarizes the key findings, significance, and implications of the research. It is the writer’s opportunity to synthesize the information presented in the paper, draw conclusions, and make recommendations for future research or actions.

The conclusion should provide a clear and concise summary of the research paper, reiterating the research question or problem, the main results, and the significance of the findings. It should also discuss the limitations of the study and suggest areas for further research.

Parts of Research Paper Conclusion

The parts of a research paper conclusion typically include:

Restatement of the Thesis

The conclusion should begin by restating the thesis statement from the introduction in a different way. This helps to remind the reader of the main argument or purpose of the research.

Summary of Key Findings

The conclusion should summarize the main findings of the research, highlighting the most important results and conclusions. This section should be brief and to the point.

Implications and Significance

In this section, the researcher should explain the implications and significance of the research findings. This may include discussing the potential impact on the field or industry, highlighting new insights or knowledge gained, or pointing out areas for future research.

Limitations and Recommendations

It is important to acknowledge any limitations or weaknesses of the research and to make recommendations for how these could be addressed in future studies. This shows that the researcher is aware of the potential limitations of their work and is committed to improving the quality of research in their field.

Concluding Statement

The conclusion should end with a strong concluding statement that leaves a lasting impression on the reader. This could be a call to action, a recommendation for further research, or a final thought on the topic.

How to Write Research Paper Conclusion

Here are some steps you can follow to write an effective research paper conclusion:

  • Restate the research problem or question: Begin by restating the research problem or question that you aimed to answer in your research. This will remind the reader of the purpose of your study.
  • Summarize the main points: Summarize the key findings and results of your research. This can be done by highlighting the most important aspects of your research and the evidence that supports them.
  • Discuss the implications: Discuss the implications of your findings for the research area and any potential applications of your research. You should also mention any limitations of your research that may affect the interpretation of your findings.
  • Provide a conclusion : Provide a concise conclusion that summarizes the main points of your paper and emphasizes the significance of your research. This should be a strong and clear statement that leaves a lasting impression on the reader.
  • Offer suggestions for future research: Lastly, offer suggestions for future research that could build on your findings and contribute to further advancements in the field.

Remember that the conclusion should be brief and to the point, while still effectively summarizing the key findings and implications of your research.

Example of Research Paper Conclusion

Here’s an example of a research paper conclusion:

Conclusion :

In conclusion, our study aimed to investigate the relationship between social media use and mental health among college students. Our findings suggest that there is a significant association between social media use and increased levels of anxiety and depression among college students. This highlights the need for increased awareness and education about the potential negative effects of social media use on mental health, particularly among college students.

Despite the limitations of our study, such as the small sample size and self-reported data, our findings have important implications for future research and practice. Future studies should aim to replicate our findings in larger, more diverse samples, and investigate the potential mechanisms underlying the association between social media use and mental health. In addition, interventions should be developed to promote healthy social media use among college students, such as mindfulness-based approaches and social media detox programs.

Overall, our study contributes to the growing body of research on the impact of social media on mental health, and highlights the importance of addressing this issue in the context of higher education. By raising awareness and promoting healthy social media use among college students, we can help to reduce the negative impact of social media on mental health and improve the well-being of young adults.

Purpose of Research Paper Conclusion

The purpose of a research paper conclusion is to provide a summary and synthesis of the key findings, significance, and implications of the research presented in the paper. The conclusion serves as the final opportunity for the writer to convey their message and leave a lasting impression on the reader.

The conclusion should restate the research problem or question, summarize the main results of the research, and explain their significance. It should also acknowledge the limitations of the study and suggest areas for future research or action.

Overall, the purpose of the conclusion is to provide a sense of closure to the research paper and to emphasize the importance of the research and its potential impact. It should leave the reader with a clear understanding of the main findings and why they matter. The conclusion serves as the writer’s opportunity to showcase their contribution to the field and to inspire further research and action.

When to Write Research Paper Conclusion

The conclusion of a research paper should be written after the body of the paper has been completed. It should not be written until the writer has thoroughly analyzed and interpreted their findings and has written a complete and cohesive discussion of the research.

Before writing the conclusion, the writer should review their research paper and consider the key points that they want to convey to the reader. They should also review the research question, hypotheses, and methodology to ensure that they have addressed all of the necessary components of the research.

Once the writer has a clear understanding of the main findings and their significance, they can begin writing the conclusion. The conclusion should be written in a clear and concise manner, and should reiterate the main points of the research while also providing insights and recommendations for future research or action.

Characteristics of Research Paper Conclusion

The characteristics of a research paper conclusion include:

  • Clear and concise: The conclusion should be written in a clear and concise manner, summarizing the key findings and their significance.
  • Comprehensive: The conclusion should address all of the main points of the research paper, including the research question or problem, the methodology, the main results, and their implications.
  • Future-oriented : The conclusion should provide insights and recommendations for future research or action, based on the findings of the research.
  • Impressive : The conclusion should leave a lasting impression on the reader, emphasizing the importance of the research and its potential impact.
  • Objective : The conclusion should be based on the evidence presented in the research paper, and should avoid personal biases or opinions.
  • Unique : The conclusion should be unique to the research paper and should not simply repeat information from the introduction or body of the paper.

Advantages of Research Paper Conclusion

The advantages of a research paper conclusion include:

  • Summarizing the key findings : The conclusion provides a summary of the main findings of the research, making it easier for the reader to understand the key points of the study.
  • Emphasizing the significance of the research: The conclusion emphasizes the importance of the research and its potential impact, making it more likely that readers will take the research seriously and consider its implications.
  • Providing recommendations for future research or action : The conclusion suggests practical recommendations for future research or action, based on the findings of the study.
  • Providing closure to the research paper : The conclusion provides a sense of closure to the research paper, tying together the different sections of the paper and leaving a lasting impression on the reader.
  • Demonstrating the writer’s contribution to the field : The conclusion provides the writer with an opportunity to showcase their contribution to the field and to inspire further research and action.

Limitations of Research Paper Conclusion

While the conclusion of a research paper has many advantages, it also has some limitations that should be considered, including:

  • I nability to address all aspects of the research: Due to the limited space available in the conclusion, it may not be possible to address all aspects of the research in detail.
  • Subjectivity : While the conclusion should be objective, it may be influenced by the writer’s personal biases or opinions.
  • Lack of new information: The conclusion should not introduce new information that has not been discussed in the body of the research paper.
  • Lack of generalizability: The conclusions drawn from the research may not be applicable to other contexts or populations, limiting the generalizability of the study.
  • Misinterpretation by the reader: The reader may misinterpret the conclusions drawn from the research, leading to a misunderstanding of the findings.

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How to Write a Conclusion for a Research Paper: Your Guide

research article conclusion

What Is a Conclusion in Research Papers

A conclusion in research paper is the final piece of the puzzle, the last chapter in the story, the grand finale of a long and arduous journey. It is the point where the researcher can finally step back and say, 'I have found what I was looking for.' But it is more than just a summary of the findings. A conclusion is a reflection on the entire research process, a chance for the researcher to evaluate the strengths and weaknesses of their methodology and to make recommendations for future research. It is a time to celebrate successes, acknowledge limitations, and offer suggestions for improvement.

You may know how to start a research paper ; however, making a compelling ending requires a thorough understanding too. A conclusion is an opportunity to connect the research findings to a larger context, discuss how the results contribute to the broader field of study and suggest possible applications in real-world scenarios. It is a moment of closure but also a starting point for new avenues of inquiry.

So, let's delve into the following sections to find out how to write a conclusion for a research paper that will leave a lasting impression on your audience.

What to Avoid in Your Research Paper Conclusion

Outline for a Research Paper Conclusion

When wondering how to make a research paper outline , the first step is to get familiar with the general structure. Here we prepared a research paper conclusion example, so let's take a close look at what information to include in a conclusion outline:

I. Summary of main findings

  • Briefly summarize the main findings of the research, including any significant results or discoveries made.

II. Restate the research question/objective

  • Restate the thesis statement or objective and indicate whether it was answered or achieved.

III. Discuss the implications of the findings

  • Discuss the implications of the findings and explain why they matter, including any practical applications or theoretical implications.

IV. Acknowledge limitations and suggest future research

  • Acknowledge any limitations or weaknesses of the study and suggest directions for future research, including any areas where further investigation is needed.

V. Concluding statement

  • Conclude your final paragraph with a statement that ties together the main points of the conclusion research paper and emphasizes their significance.

Tips on How to Make a Conclusion in Research

By following these tips, you won't have to wonder 'how to make a conclusion in research' anymore and will effectively highlight its significance.

Research Paper Conclusion

  • Emphasize the significance of the findings: When discussing the implications, emphasize the practical or theoretical implications. Use language that emphasizes the importance of the findings and how they contribute to the broader field of study. For example, 'The study findings have important implications for clinical practice and highlight the need for further research in this area.'
  • Tie back to the introduction: When concluding, tie the findings back to the introduction by reminding readers of the original purpose of the research. This helps to provide closure to the research and emphasizes the significance of the findings. For example, 'This study has successfully answered the research question of whether stress is a risk factor for heart disease in middle-aged adults, and provides important insights into the relationship between stress and cardiovascular health.'
  • Avoid introducing new information: It's important to avoid introducing new information in the conclusion, as this can confuse readers and detract from the key arguments of the research. Stick to summarizing the main findings, discussing the implications, acknowledging limitations, and suggesting future research possibilities.
  • Use clear and concise language: When making a conclusion, use clear and concise language. Avoid using technical jargon or overly complex language; instead, focus on using language accessible to a broad audience.
  • End with a strong concluding statement: End your paper's conclusion with a strong concluding statement that ties together the main points and emphasizes their significance. This provides closure to the research and leaves readers with a lasting impression. Here is a conclusion in research example: 'Overall, the findings of this study provide important insights into the relationship between X and Y and highlight the need for further research in this area.'

How to Develop a Compelling Conclusion

Here are some main points to help you not just summarize the key thoughts of your work, but to go deeper to warrant a better grade:

  • If you have been writing about a contemporary problem, talk about what can happen if the problem is not solved, but do not add new information. Do not bring in new evidence or new facts.
  • Don’t hesitate to offer or to recommend some course of action.
  • Use relevant quotations or expert opinions to make your conclusion more authoritative.
  • Repeat a key statistic, fact, or even a visual image that represents the main point of your paper.
  • Express personal reflection. You can even talk about your own life experiences.
  • Interpret the results in your own way to give them a fresh perspective. Do not be afraid to be a researcher who introduces something new—even for the most common problems.
  • Finish your conclusions with a short, but powerful message which will help others remember your study. This message is something that can differentiate you from others.
  • Do not say "in conclusion" or similar sayings. This includes "in summary" or "in closing." Why? These sayings sound a bit unnatural and stiff. They make your work appear too formal and pragmatic. A strong conclusion does not need the word - “In conclusion”. It will stand on its own.
  • Use the same consistent tone through your entire paper. It sounds unnatural if you suddenly use an absolutely different tone or style of presenting the information.
  • Check your entire paper to make sure that you have not left any really important points behind.

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How to Make a Conclusion Effective Rhetorically

Here are some unique tips on how to start conclusion in research rhetorically from our service:

  • Use rhetorical questions : Rhetorical questions are a powerful tool that can help to engage readers and prompt them to think critically about the research. For example, 'What impact will these findings have on the field of X? How can we use these findings to improve clinical practice?'
  • Use strong language: Using strong, impactful language can help emphasize the research's significance and leave a lasting impression on readers. For example, 'These findings have the potential to revolutionize the way we approach X, and could have far-reaching implications for future research in this area.'
  • Use repetition: Repetition can be an effective rhetorical tool that can help to reinforce key points and leave a lasting impression on readers. For example, repeating a phrase such as 'These findings underscore the importance of...' can help emphasize the research's significance.
  • Use anecdotes : Using anecdotes or stories can help to make the research more relatable and engaging for readers. For example, sharing a personal story or case study that illustrates the research's practical applications can help emphasize its significance.
  • Use vivid imagery : It can help bring the research to life and make it more memorable for readers. For example, using descriptive language to describe the impact of the research, such as 'This study sheds new light on X, illuminating a path forward for researchers in this field.'

Making a Conclusion Effective Logically

By using these logical strategies from our custom dissertation writing , you can make your research paper conclusion more coherent, persuasive, and effective.

  • Use logical transitions : To make the conclusion flow smoothly and logically, use transition words and phrases such as 'therefore,' 'thus,' 'consequently,' and 'in conclusion.' This helps to signal to readers that the conclusion is a logical extension of the research that has been presented.
  • Summarize key findings in order : To make the conclusion logical, summarize the key findings of the research in the order in which they were presented. This helps readers follow the research's progression and understand how the various findings fit together.
  • Address potential counterarguments: Researchers can demonstrate a thorough and logical approach to their research by acknowledging and addressing these potential criticisms.
  • Use quantitative data: This helps provide concrete evidence for the conclusions being drawn and makes the research more convincing.
  • Provide a clear and concise summary: This helps readers understand the main takeaways from the research and provides a logical conclusion.

Things to Avoid in the Conclusion of Your Research Paper

By avoiding these common pitfalls, you can ensure that their conclusions are clear, concise, and effective in summarizing their research's main findings and implications.

Avoid in Your Research Paper Conclusion

  • Don't introduce new information: The conclusion is not the place to introduce new information or data that was not discussed in the main body of the paper. Stick to summarizing the key findings and insights that were already presented.
  • Don't repeat information : While it's important to summarize key findings in the example of conclusion in research paper, don't simply repeat information already presented earlier. Instead, focus on synthesizing and connecting the various findings in a new way.
  • Don't make unsupported claims: Avoid making sweeping or unsupported claims in the conclusion. Make sure that all conclusions are backed up by the data and evidence presented in the main body of the paper.
  • Don't be overly emotional: While being passionate about your research topic is important, avoid being overly emotional or sentimental in the conclusion. Stick to a professional and objective tone.
  • Don't end abruptly: Don't end the conclusion of research paper abruptly without providing a clear sense of closure. Instead, summarize the main points and insights, and consider ending with a call to action or a suggestion for future research.

Research Paper Conclusion Example

That’s pretty much everything you need to know about how to summarize a research paper. There are two things left: to take a look at the research paper conclusion example from our team.

If you liked the sample, you might also be interested in a research proposal example APA . And if you'd rather have experts handle the writing for you, contact us today! We provide writing, editing, and proofreading help to anyone who needs a quick solution to academic stress. Just send us your request and buy a research paper easy.

Final Thoughts

Now that you know what is a conclusion in research, you can agree that it requires careful consideration and planning. By following the general rules and tips outlined in this article, researchers can write paper that effectively summarizes the key findings and insights of their research in a logical and rhetorically effective manner.

At EssayPro, we offer a range of writing services to help researchers and students succeed in their academic pursuits. Whether you need help with writing academic research papers, editing, or proofreading, we have the expertise and skills to help you achieve your goals.

So why wait? Contact our professional essay writers today to learn more about our services and how we can help you succeed in your academic and professional endeavors. Let us help you craft an effective research paper conclusion sample that will leave a lasting impression on your readers and elevate the impact of your research.

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How to Write a Conclusion for a Research Paper

Sumalatha G

Table of Contents

Writing a conclusion for a research paper is a critical step that often determines the overall impact and impression the paper leaves on the reader. While some may view the conclusion as a mere formality, it is actually an opportunity to wrap up the main points, provide closure, and leave a lasting impression. In this article, we will explore the importance of a well-crafted conclusion and discuss various tips and strategies to help you write an engaging and impactful conclusion for your research paper.


Before delving into the specifics of writing a conclusion, it is important to understand why it is such a crucial component of a research paper. The conclusion serves to summarize the main points of the paper and reemphasize their significance. A well-written conclusion can leave the reader satisfied and inspired, while a poorly executed one may undermine the credibility of the entire paper. Therefore, it is essential to give careful thought and attention to crafting an effective conclusion.

When writing a research paper, the conclusion acts as the final destination for the reader. It is the point where all the information, arguments, and evidence presented throughout the paper converge. Just as a traveler reaches the end of a journey, the reader reaches the conclusion to find closure and a sense of fulfillment. This is why the conclusion should not be taken lightly; it is a critical opportunity to leave a lasting impact on the reader.

Moreover, the conclusion is not merely a repetition of the introduction or a summary of the main points. It goes beyond that by providing a deeper understanding of the research findings and their implications. It allows the writer to reflect on the significance of their work and its potential contributions to the field. By doing so, the conclusion elevates the research paper from a mere collection of facts to a thought-provoking piece of scholarship.

In the following sections, we will explore various strategies and techniques for crafting a compelling conclusion. By understanding the importance of the conclusion and learning how to write one effectively, you will be equipped to create impactful research papers.

Structuring the Conclusion

In order to create an effective conclusion, it is important to consider its structure. A well-structured conclusion should begin by restating the thesis statement and summarizing the main points of the paper. It should then move on to provide a concise synthesis of the key findings and arguments, highlighting their implications and relevance. Finally, the conclusion should end with a thought-provoking statement that leaves the reader with a lasting impression.

Additionally, using phrases like "this research demonstrates," "the findings show," or "it is clear that" can help to highlight the significance of your research and emphasize your main conclusions.

Tips for Writing an Engaging Conclusion

Writing an engaging conclusion requires careful consideration and attention to detail. Here are some tips to help you create an impactful conclusion for your research paper:

  • Revisit the Introduction: Start your conclusion by referencing your introduction. Remind the reader of the research question or problem you initially posed and show how your research has addressed it.
  • Summarize Your Main Points: Provide a concise summary of the main points and arguments presented in your paper. Be sure to restate your thesis statement and highlight the key findings.
  • Offer a Fresh Perspective: Use the conclusion as an opportunity to provide a fresh perspective or offer insights that go beyond the main body of the paper. This will leave the reader with something new to consider.
  • Leave a Lasting Impression: End your conclusion with a thought-provoking statement or a call to action. This will leave a lasting impression on the reader and encourage further exploration of the research topic.

Addressing Counter Arguments In Conclusion

While crafting your conclusion, you can address any potential counterarguments or limitations of your research. This will demonstrate that you have considered alternative perspectives and have taken them into account in your conclusions. By acknowledging potential counterarguments, you can strengthen the credibility and validity of your research. And by openly discussing limitations, you demonstrate transparency and honesty in your research process.

Language and Tone To Be Used In Conclusion

The language and tone of your conclusion play a crucial role in shaping the overall impression of your research paper. It is important to use clear and concise language that is appropriate for the academic context. Avoid using overly informal or colloquial language that may undermine the credibility of your research. Additionally, consider the tone of your conclusion – it should be professional, confident, and persuasive, while still maintaining a respectful and objective tone.

When it comes to the language used in your conclusion, precision is key. You want to ensure that your ideas are communicated effectively and that there is no room for misinterpretation. Using clear and concise language will not only make your conclusion easier to understand but will also demonstrate your command of the subject matter.

Furthermore, it is important to strike the right balance between formality and accessibility. While academic writing typically requires a more formal tone, you should still aim to make your conclusion accessible to a wider audience. This means avoiding jargon or technical terms that may confuse readers who are not familiar with the subject matter. Instead, opt for language that is clear and straightforward, allowing anyone to grasp the main points of your research.

Another aspect to consider is the tone of your conclusion. The tone should reflect the confidence you have in your research findings and the strength of your argument. By adopting a professional and confident tone, you are more likely to convince your readers of the validity and importance of your research. However, it is crucial to strike a balance and avoid sounding arrogant or dismissive of opposing viewpoints. Maintaining a respectful and objective tone will help you engage with your audience in a more persuasive manner.

Moreover, the tone of your conclusion should align with the overall tone of your research paper. Consistency in tone throughout your paper will create a cohesive and unified piece of writing.

Common Mistakes to Avoid While Writing a Conclusion

When writing a conclusion, there are several common mistakes that researchers often make. By being aware of these pitfalls, you can avoid them and create a more effective conclusion for your research paper. Some common mistakes include:

  • Repeating the Introduction: A conclusion should not simply be a reworded version of the introduction. While it is important to revisit the main points, try to present them in a fresh and broader perspective, by foregrounding the implications/impacts of your research.
  • Introducing New Information: The conclusion should not introduce any new information or arguments. Instead, it should focus on summarizing and synthesizing the main points presented in the paper.
  • Being Vague or General: Avoid using vague or general statements in your conclusion. Instead, be specific and provide concrete examples or evidence to support your main points.
  • Ending Abruptly: A conclusion should provide a sense of closure and completeness. Avoid ending your conclusion abruptly or leaving the reader with unanswered questions.

Editing and Revising the Conclusion

Just like the rest of your research paper, the conclusion should go through a thorough editing and revising process. This will help to ensure clarity, coherence, and impact in the conclusion. As you revise your conclusion, consider the following:

  • Check for Consistency: Ensure that your conclusion aligns with the main body of the paper and does not introduce any new or contradictory information.
  • Eliminate Redundancy: Remove any repetitive or redundant information in your conclusion. Instead, focus on presenting the key points in a concise and engaging manner.
  • Proofread for Clarity: Read your conclusion aloud or ask someone else to read it to ensure that it is clear and understandable. Check for any grammatical or spelling errors that may distract the reader.
  • Seek Feedback: Consider sharing your conclusion with peers or mentors to get their feedback and insights. This can help you strengthen your conclusion and make it more impactful.

How to Write Conclusion as a Call to Action

Finally, consider using your conclusion as a call to action. Encourage the reader to take further action, such as conducting additional research or considering the implications of your findings. By providing a clear call to action, you can inspire the reader to actively engage with your research and continue the conversation on the topic.

Adapting to Different Research Paper Types

It is important to adapt your conclusion approach based on the type of research paper you are writing. Different research paper types may require different strategies and approaches to writing the conclusion. For example, a scientific research paper may focus more on summarizing the key findings and implications, while a persuasive research paper may emphasize the call to action and the potential impact of the research. Tailor your conclusion to suit the specific goals and requirements of your research paper.

Final Thoughts

A well-crafted conclusion can leave a lasting impression on the reader and enhance the impact of your research. By following the tips and strategies outlined in this article, you can create an engaging and impactful conclusion that effectively summarizes your main points, addresses potential counterarguments, and leaves the reader with a sense of closure and inspiration. Embrace the importance of the conclusion and view it as an opportunity to showcase the significance and relevance of your research.

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How to Write a Conclusion for a Research Paper

Last Updated: June 29, 2023 Approved

This article was co-authored by Christopher Taylor, PhD . Christopher Taylor is an Adjunct Assistant Professor of English at Austin Community College in Texas. He received his PhD in English Literature and Medieval Studies from the University of Texas at Austin in 2014. wikiHow marks an article as reader-approved once it receives enough positive feedback. This article received 42 testimonials and 82% of readers who voted found it helpful, earning it our reader-approved status. This article has been viewed 2,252,687 times.

The conclusion of a research paper needs to summarize the content and purpose of the paper without seeming too wooden or dry. Every basic conclusion must share several key elements, but there are also several tactics you can play around with to craft a more effective conclusion and several you should avoid to prevent yourself from weakening your paper's conclusion. Here are some writing tips to keep in mind when creating a conclusion for your next research paper.

Sample Conclusions

Writing a basic conclusion.

Step 1 Restate the topic.

  • Do not spend a great amount of time or space restating your topic.
  • A good research paper will make the importance of your topic apparent, so you do not need to write an elaborate defense of your topic in the conclusion.
  • Usually a single sentence is all you need to restate your topic.
  • An example would be if you were writing a paper on the epidemiology of infectious disease, you might say something like "Tuberculosis is a widespread infectious disease that affects millions of people worldwide every year."
  • Yet another example from the humanities would be a paper about the Italian Renaissance: "The Italian Renaissance was an explosion of art and ideas centered around artists, writers, and thinkers in Florence."

Step 2 Restate your thesis.

  • A thesis is a narrowed, focused view on the topic at hand.
  • This statement should be rephrased from the thesis you included in your introduction. It should not be identical or too similar to the sentence you originally used.
  • Try re-wording your thesis statement in a way that complements your summary of the topic of your paper in your first sentence of your conclusion.
  • An example of a good thesis statement, going back to the paper on tuberculosis, would be "Tuberculosis is a widespread disease that affects millions of people worldwide every year. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease ."

Step 3 Briefly summarize your main points.

  • A good way to go about this is to re-read the topic sentence of each major paragraph or section in the body of your paper.
  • Find a way to briefly restate each point mentioned in each topic sentence in your conclusion. Do not repeat any of the supporting details used within your body paragraphs.
  • Under most circumstances, you should avoid writing new information in your conclusion. This is especially true if the information is vital to the argument or research presented in your paper.
  • For example, in the TB paper you could summarize the information. "Tuberculosis is a widespread disease that affects millions of people worldwide. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease. In developing countries, such as those in Africa and Southeast Asia, the rate of TB infections is soaring. Crowded conditions, poor sanitation, and lack of access to medical care are all compounding factors in the spread of the disease. Medical experts, such as those from the World Health Organization are now starting campaigns to go into communities in developing countries and provide diagnostic testing and treatments. However, the treatments for TB are very harsh and have many side effects. This leads to patient non-compliance and spread of multi-drug resistant strains of the disease."

Step 4 Add the points up.

  • Note that this is not needed for all research papers.
  • If you already fully explained what the points in your paper mean or why they are significant, you do not need to go into them in much detail in your conclusion. Simply restating your thesis or the significance of your topic should suffice.
  • It is always best practice to address important issues and fully explain your points in the body of your paper. The point of a conclusion to a research paper is to summarize your argument for the reader and, perhaps, to call the reader to action if needed.

Step 5 Make a call to action when appropriate.

  • Note that a call for action is not essential to all conclusions. A research paper on literary criticism, for instance, is less likely to need a call for action than a paper on the effect that television has on toddlers and young children.
  • A paper that is more likely to call readers to action is one that addresses a public or scientific need. Let's go back to our example of tuberculosis. This is a very serious disease that is spreading quickly and with antibiotic-resistant forms.
  • A call to action in this research paper would be a follow-up statement that might be along the lines of "Despite new efforts to diagnose and contain the disease, more research is needed to develop new antibiotics that will treat the most resistant strains of tuberculosis and ease the side effects of current treatments."

Step 6 Answer the “so what” question.

  • For example, if you are writing a history paper, then you might discuss how the historical topic you discussed matters today. If you are writing about a foreign country, then you might use the conclusion to discuss how the information you shared may help readers understand their own country.

Making Your Conclusion as Effective as Possible

Step 1 Stick with a basic synthesis of information.

  • Since this sort of conclusion is so basic, you must aim to synthesize the information rather than merely summarizing it.
  • Instead of merely repeating things you already said, rephrase your thesis and supporting points in a way that ties them all together.
  • By doing so, you make your research paper seem like a "complete thought" rather than a collection of random and vaguely related ideas.

Step 2 Bring things full circle.

  • Ask a question in your introduction. In your conclusion, restate the question and provide a direct answer.
  • Write an anecdote or story in your introduction but do not share the ending. Instead, write the conclusion to the anecdote in the conclusion of your paper.
  • For example, if you wanted to get more creative and put a more humanistic spin on a paper on tuberculosis, you might start your introduction with a story about a person with the disease, and refer to that story in your conclusion. For example, you could say something like this before you re-state your thesis in your conclusion: "Patient X was unable to complete the treatment for tuberculosis due to severe side effects and unfortunately succumbed to the disease."
  • Use the same concepts and images introduced in your introduction in your conclusion. The images may or may not appear at other points throughout the research paper.

Step 3 Close with logic.

  • Include enough information about your topic to back the statement up but do not get too carried away with excess detail.
  • If your research did not provide you with a clear-cut answer to a question posed in your thesis, do not be afraid to indicate as much.
  • Restate your initial hypothesis and indicate whether you still believe it or if the research you performed has begun swaying your opinion.
  • Indicate that an answer may still exist and that further research could shed more light on the topic at hand.

Step 4 Pose a question.

  • This may not be appropriate for all types of research papers. Most research papers, such as one on effective treatment for diseases, will have the information to make the case for a particular argument already in the paper.
  • A good example of a paper that might ask a question of the reader in the ending is one about a social issue, such as poverty or government policy.
  • Ask a question that will directly get at the heart or purpose of the paper. This question is often the same question, or some version of it, that you may have started with when you began your research.
  • Make sure that the question can be answered by the evidence presented in your paper.
  • If desired you can briefly summarize the answer after stating the question. You could also leave the question hanging for the reader to answer, though.

Step 5 Make a suggestion.

  • Even without a call to action, you can still make a recommendation to your reader.
  • For instance, if you are writing about a topic like third-world poverty, you can various ways for the reader to assist in the problem without necessarily calling for more research.
  • Another example would be, in a paper about treatment for drug-resistant tuberculosis, you could suggest donating to the World Health Organization or research foundations that are developing new treatments for the disease.

Avoiding Common Pitfalls

Step 1 Avoid saying

  • These sayings usually sound stiff, unnatural, or trite when used in writing.
  • Moreover, using a phrase like "in conclusion" to begin your conclusion is a little too straightforward and tends to lead to a weak conclusion. A strong conclusion can stand on its own without being labeled as such.

Step 2 Do not wait until the conclusion to state your thesis.

  • Always state the main argument or thesis in the introduction. A research paper is an analytical discussion of an academic topic, not a mystery novel.
  • A good, effective research paper will allow your reader to follow your main argument from start to finish.
  • This is why it is best practice to start your paper with an introduction that states your main argument and to end the paper with a conclusion that re-states your thesis for re-iteration.

Step 3 Leave out new information.

  • All significant information should be introduced in the body of the paper.
  • Supporting evidence expands the topic of your paper by making it appear more detailed. A conclusion should narrow the topic to a more general point.
  • A conclusion should only summarize what you have already stated in the body of your paper.
  • You may suggest further research or a call to action, but you should not bring in any new evidence or facts in the conclusion.

Step 4 Avoid changing the tone of the paper.

  • Most often, a shift in tone occurs when a research paper with an academic tone gives an emotional or sentimental conclusion.
  • Even if the topic of the paper is of personal significance for you, you should not indicate as much in your paper.
  • If you want to give your paper a more humanistic slant, you could start and end your paper with a story or anecdote that would give your topic more personal meaning to the reader.
  • This tone should be consistent throughout the paper, however.

Step 5 Make no apologies.

  • Apologetic statements include phrases like "I may not be an expert" or "This is only my opinion."
  • Statements like this can usually be avoided by refraining from writing in the first-person.
  • Avoid any statements in the first-person. First-person is generally considered to be informal and does not fit with the formal tone of a research paper.

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About This Article

Christopher Taylor, PhD

To write a conclusion for a research paper, start by restating your thesis statement to remind your readers what your main topic is and bring everything full circle. Then, briefly summarize all of the main points you made throughout your paper, which will help remind your readers of everything they learned. You might also want to include a call to action if you think more research or work needs to be done on your topic by writing something like, "Despite efforts to contain the disease, more research is needed to develop antibiotics." Finally, end your conclusion by explaining the broader context of your topic and why your readers should care about it, which will help them understand why your topic is relevant and important. For tips from our Academic co-author, like how to avoid common pitfalls when writing your conclusion, scroll down! Did this summary help you? Yes No

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How to Write a Thesis or Dissertation Conclusion

Published on September 6, 2022 by Tegan George and Shona McCombes. Revised on November 20, 2023.

The conclusion is the very last part of your thesis or dissertation . It should be concise and engaging, leaving your reader with a clear understanding of your main findings, as well as the answer to your research question .

In it, you should:

  • Clearly state the answer to your main research question
  • Summarize and reflect on your research process
  • Make recommendations for future work on your thesis or dissertation topic
  • Show what new knowledge you have contributed to your field
  • Wrap up your thesis or dissertation

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Table of contents

Discussion vs. conclusion, how long should your conclusion be, step 1: answer your research question, step 2: summarize and reflect on your research, step 3: make future recommendations, step 4: emphasize your contributions to your field, step 5: wrap up your thesis or dissertation, full conclusion example, conclusion checklist, other interesting articles, frequently asked questions about conclusion sections.

While your conclusion contains similar elements to your discussion section , they are not the same thing.

Your conclusion should be shorter and more general than your discussion. Instead of repeating literature from your literature review , discussing specific research results , or interpreting your data in detail, concentrate on making broad statements that sum up the most important insights of your research.

As a rule of thumb, your conclusion should not introduce new data, interpretations, or arguments.

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Depending on whether you are writing a thesis or dissertation, your length will vary. Generally, a conclusion should make up around 5–7% of your overall word count.

An empirical scientific study will often have a short conclusion, concisely stating the main findings and recommendations for future research. A humanities dissertation topic or systematic review , on the other hand, might require more space to conclude its analysis, tying all the previous sections together in an overall argument.

Your conclusion should begin with the main question that your thesis or dissertation aimed to address. This is your final chance to show that you’ve done what you set out to do, so make sure to formulate a clear, concise answer.

  • Don’t repeat a list of all the results that you already discussed
  • Do synthesize them into a final takeaway that the reader will remember.

An empirical thesis or dissertation conclusion may begin like this:

A case study –based thesis or dissertation conclusion may begin like this:

In the second example, the research aim is not directly restated, but rather added implicitly to the statement. To avoid repeating yourself, it is helpful to reformulate your aims and questions into an overall statement of what you did and how you did it.

Your conclusion is an opportunity to remind your reader why you took the approach you did, what you expected to find, and how well the results matched your expectations.

To avoid repetition , consider writing more reflectively here, rather than just writing a summary of each preceding section. Consider mentioning the effectiveness of your methodology , or perhaps any new questions or unexpected insights that arose in the process.

You can also mention any limitations of your research, but only if you haven’t already included these in the discussion. Don’t dwell on them at length, though—focus on the positives of your work.

  • While x limits the generalizability of the results, this approach provides new insight into y .
  • This research clearly illustrates x , but it also raises the question of y .

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See an example

research article conclusion

You may already have made a few recommendations for future research in your discussion section, but the conclusion is a good place to elaborate and look ahead, considering the implications of your findings in both theoretical and practical terms.

  • Based on these conclusions, practitioners should consider …
  • To better understand the implications of these results, future studies could address …
  • Further research is needed to determine the causes of/effects of/relationship between …

When making recommendations for further research, be sure not to undermine your own work. Relatedly, while future studies might confirm, build on, or enrich your conclusions, they shouldn’t be required for your argument to feel complete. Your work should stand alone on its own merits.

Just as you should avoid too much self-criticism, you should also avoid exaggerating the applicability of your research. If you’re making recommendations for policy, business, or other practical implementations, it’s generally best to frame them as “shoulds” rather than “musts.” All in all, the purpose of academic research is to inform, explain, and explore—not to demand.

Make sure your reader is left with a strong impression of what your research has contributed to the state of your field.

Some strategies to achieve this include:

  • Returning to your problem statement to explain how your research helps solve the problem
  • Referring back to the literature review and showing how you have addressed a gap in knowledge
  • Discussing how your findings confirm or challenge an existing theory or assumption

Again, avoid simply repeating what you’ve already covered in the discussion in your conclusion. Instead, pick out the most important points and sum them up succinctly, situating your project in a broader context.

The end is near! Once you’ve finished writing your conclusion, it’s time to wrap up your thesis or dissertation with a few final steps:

  • It’s a good idea to write your abstract next, while the research is still fresh in your mind.
  • Next, make sure your reference list is complete and correctly formatted. To speed up the process, you can use our free APA citation generator .
  • Once you’ve added any appendices , you can create a table of contents and title page .
  • Finally, read through the whole document again to make sure your thesis is clearly written and free from language errors. You can proofread it yourself , ask a friend, or consider Scribbr’s proofreading and editing service .

Here is an example of how you can write your conclusion section. Notice how it includes everything mentioned above:

V. Conclusion

The current research aimed to identify acoustic speech characteristics which mark the beginning of an exacerbation in COPD patients.

The central questions for this research were as follows: 1. Which acoustic measures extracted from read speech differ between COPD speakers in stable condition and healthy speakers? 2. In what ways does the speech of COPD patients during an exacerbation differ from speech of COPD patients during stable periods?

All recordings were aligned using a script. Subsequently, they were manually annotated to indicate respiratory actions such as inhaling and exhaling. The recordings of 9 stable COPD patients reading aloud were then compared with the recordings of 5 healthy control subjects reading aloud. The results showed a significant effect of condition on the number of in- and exhalations per syllable, the number of non-linguistic in- and exhalations per syllable, and the ratio of voiced and silence intervals. The number of in- and exhalations per syllable and the number of non-linguistic in- and exhalations per syllable were higher for COPD patients than for healthy controls, which confirmed both hypotheses.

However, the higher ratio of voiced and silence intervals for COPD patients compared to healthy controls was not in line with the hypotheses. This unpredicted result might have been caused by the different reading materials or recording procedures for both groups, or by a difference in reading skills. Moreover, there was a trend regarding the effect of condition on the number of syllables per breath group. The number of syllables per breath group was higher for healthy controls than for COPD patients, which was in line with the hypothesis. There was no effect of condition on pitch, intensity, center of gravity, pitch variability, speaking rate, or articulation rate.

This research has shown that the speech of COPD patients in exacerbation differs from the speech of COPD patients in stable condition. This might have potential for the detection of exacerbations. However, sustained vowels rarely occur in spontaneous speech. Therefore, the last two outcome measures might have greater potential for the detection of beginning exacerbations, but further research on the different outcome measures and their potential for the detection of exacerbations is needed due to the limitations of the current study.

Checklist: Conclusion

I have clearly and concisely answered the main research question .

I have summarized my overall argument or key takeaways.

I have mentioned any important limitations of the research.

I have given relevant recommendations .

I have clearly explained what my research has contributed to my field.

I have  not introduced any new data or arguments.

You've written a great conclusion! Use the other checklists to further improve your dissertation.

If you want to know more about AI for academic writing, AI tools, or research bias, make sure to check out some of our other articles with explanations and examples or go directly to our tools!

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In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

While it may be tempting to present new arguments or evidence in your thesis or disseration conclusion , especially if you have a particularly striking argument you’d like to finish your analysis with, you shouldn’t. Theses and dissertations follow a more formal structure than this.

All your findings and arguments should be presented in the body of the text (more specifically in the discussion section and results section .) The conclusion is meant to summarize and reflect on the evidence and arguments you have already presented, not introduce new ones.

For a stronger dissertation conclusion , avoid including:

  • Important evidence or analysis that wasn’t mentioned in the discussion section and results section
  • Generic concluding phrases (e.g. “In conclusion …”)
  • Weak statements that undermine your argument (e.g., “There are good points on both sides of this issue.”)

Your conclusion should leave the reader with a strong, decisive impression of your work.

The conclusion of your thesis or dissertation shouldn’t take up more than 5–7% of your overall word count.

The conclusion of your thesis or dissertation should include the following:

  • A restatement of your research question
  • A summary of your key arguments and/or results
  • A short discussion of the implications of your research

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George, T. & McCombes, S. (2023, November 20). How to Write a Thesis or Dissertation Conclusion. Scribbr. Retrieved February 22, 2024, from

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OASIS: Writing Center

Writing a paper: conclusions, writing a conclusion.

A conclusion is an important part of the paper; it provides closure for the reader while reminding the reader of the contents and importance of the paper. It accomplishes this by stepping back from the specifics in order to view the bigger picture of the document. In other words, it is reminding the reader of the main argument. For most course papers, it is usually one paragraph that simply and succinctly restates the main ideas and arguments, pulling everything together to help clarify the thesis of the paper. A conclusion does not introduce new ideas; instead, it should clarify the intent and importance of the paper. It can also suggest possible future research on the topic.

An Easy Checklist for Writing a Conclusion

It is important to remind the reader of the thesis of the paper so he is reminded of the argument and solutions you proposed.
Think of the main points as puzzle pieces, and the conclusion is where they all fit together to create a bigger picture. The reader should walk away with the bigger picture in mind.
Make sure that the paper places its findings in the context of real social change.
Make sure the reader has a distinct sense that the paper has come to an end. It is important to not leave the reader hanging. (You don’t want her to have flip-the-page syndrome, where the reader turns the page, expecting the paper to continue. The paper should naturally come to an end.)
No new ideas should be introduced in the conclusion. It is simply a review of the material that is already present in the paper. The only new idea would be the suggesting of a direction for future research.

Conclusion Example

As addressed in my analysis of recent research, the advantages of a later starting time for high school students significantly outweigh the disadvantages. A later starting time would allow teens more time to sleep--something that is important for their physical and mental health--and ultimately improve their academic performance and behavior. The added transportation costs that result from this change can be absorbed through energy savings. The beneficial effects on the students’ academic performance and behavior validate this decision, but its effect on student motivation is still unknown. I would encourage an in-depth look at the reactions of students to such a change. This sort of study would help determine the actual effects of a later start time on the time management and sleep habits of students.

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How to Write a Research Paper Conclusion Section

research article conclusion

What is a conclusion in a research paper?

The conclusion in a research paper is the final paragraph or two in a research paper. In scientific papers, the conclusion usually follows the Discussion section , summarizing the importance of the findings and reminding the reader why the work presented in the paper is relevant.

However, it can be a bit confusing to distinguish the conclusion section/paragraph from a summary or a repetition of your findings, your own opinion, or the statement of the implications of your work. In fact, the conclusion should contain a bit of all of these other parts but go beyond it—but not too far beyond! 

The structure and content of the conclusion section can also vary depending on whether you are writing a research manuscript or an essay. This article will explain how to write a good conclusion section, what exactly it should (and should not) contain, how it should be structured, and what you should avoid when writing it.  

Table of Contents:

What does a good conclusion section do, what to include in a research paper conclusion.

  • Conclusion in an Essay
  • Research Paper Conclusion 
  • Conclusion Paragraph Outline and Example
  • What Not to Do When Writing a Conclusion

The conclusion of a research paper has several key objectives. It should:

  • Restate your research problem addressed in the introduction section
  • Summarize your main arguments, important findings, and broader implications
  • Synthesize key takeaways from your study

The specific content in the conclusion depends on whether your paper presents the results of original scientific research or constructs an argument through engagement with previously published sources.

You presented your general field of study to the reader in the introduction section, by moving from general information (the background of your work, often combined with a literature review ) to the rationale of your study and then to the specific problem or topic you addressed, formulated in the form of the statement of the problem in research or the thesis statement in an essay.

In the conclusion section, in contrast, your task is to move from your specific findings or arguments back to a more general depiction of how your research contributes to the readers’ understanding of a certain concept or helps solve a practical problem, or fills an important gap in the literature. The content of your conclusion section depends on the type of research you are doing and what type of paper you are writing. But whatever the outcome of your work is, the conclusion is where you briefly summarize it and place it within a larger context. It could be called the “take-home message” of the entire paper.

What to summarize in the conclusion

Your conclusion section needs to contain a very brief summary of your work , a very brief summary of the main findings of your work, and a mention of anything else that seems relevant when you now look at your work from a bigger perspective, even if it was not initially listed as one of your main research questions. This could be a limitation, for example, a problem with the design of your experiment that either needs to be considered when drawing any conclusions or that led you to ask a different question and therefore draw different conclusions at the end of your study (compared to when you started out).

Once you have reminded the reader of what you did and what you found, you need to go beyond that and also provide either your own opinion on why your work is relevant (and for whom, and how) or theoretical or practical implications of the study , or make a specific call for action if there is one to be made.   

How to Write an Essay Conclusion

Academic essays follow quite different structures than their counterparts in STEM and the natural sciences. Humanities papers often have conclusion sections that are much longer and contain more detail than scientific papers. There are three main types of academic essay conclusions.

Summarizing conclusion

The most typical conclusion at the end of an analytical/explanatory/argumentative essay is a summarizing conclusion . This is, as the name suggests, a clear summary of the main points of your topic and thesis. Since you might have gone through a number of different arguments or subtopics in the main part of your essay, you need to remind the reader again what those were, how they fit into each other, and how they helped you develop or corroborate your hypothesis.

For an essay that analyzes how recruiters can hire the best candidates in the shortest time or on “how starving yourself will increase your lifespan, according to science”, a summary of all the points you discussed might be all you need. Note that you should not exactly repeat what you said earlier, but rather highlight the essential details and present those to your reader in a different way. 

Externalizing conclusion

If you think that just reminding the reader of your main points is not enough, you can opt for an externalizing conclusion instead, that presents new points that were not presented in the paper so far. These new points can be additional facts and information or they can be ideas that are relevant to the topic and have not been mentioned before.

Such a conclusion can stimulate your readers to think about your topic or the implications of your analysis in a whole new way. For example, at the end of a historical analysis of a specific event or development, you could direct your reader’s attention to some current events that were not the topic of your essay but that provide a different context for your findings.

Editorial conclusion

In an editorial conclusion , another common type of conclusion that you will find at the end of papers and essays, you do not add new information but instead present your own experiences or opinions on the topic to round everything up. What makes this type of conclusion interesting is that you can choose to agree or disagree with the information you presented in your paper so far. For example, if you have collected and analyzed information on how a specific diet helps people lose weight, you can nevertheless have your doubts on the sustainability of that diet or its practicability in real life—if such arguments were not included in your original thesis and have therefore not been covered in the main part of your paper, the conclusion section is the place where you can get your opinion across.    

How to Conclude an Empirical Research Paper

An empirical research paper is usually more concise and succinct than an essay, because, if it is written well, it focuses on one specific question, describes the method that was used to answer that one question, describes and explains the results, and guides the reader in a logical way from the introduction to the discussion without going on tangents or digging into not absolutely relevant topics.

Summarize the findings

In a scientific paper, you should include a summary of the findings. Don’t go into great detail here (you will have presented your in-depth  results  and  discussion  already), but do clearly express the answers to the  research questions  you investigated.

Describe your main findings, even if they weren’t necessarily the ones anticipated, and explain the conclusion they led you to. Explain these findings in as few words as possible.

Instead of beginning with “ In conclusion, in this study, we investigated the effect of stress on the brain using fMRI …”, you should try to find a way to incorporate the repetition of the essential (and only the essential) details into the summary of the key points. “ The findings of this fMRI study on the effect of stress on the brain suggest that …” or “ While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study show that, surprisingly… ” would be better ways to start a conclusion. 

You should also not bring up new ideas or present new facts in the conclusion of a research paper, but stick to the background information you have presented earlier, to the findings you have already discussed, and the limitations and implications you have already described. The one thing you can add here is a practical recommendation that you haven’t clearly stated before—but even that one needs to follow logically from everything you have already discussed in the discussion section.

Discuss the implications

After summing up your key arguments or findings, conclude the paper by stating the broader implications of the research , whether in methods , approach, or findings. Express practical or theoretical takeaways from your paper. This often looks like a “call to action” or a final “sales pitch” that puts an exclamation point on your paper.

If your research topic is more theoretical in nature, your closing statement should express the significance of your argument—for example, in proposing a new understanding of a topic or laying the groundwork for future research.

Future research example

Future research into education standards should focus on establishing a more detailed picture of how novel pedagogical approaches impact young people’s ability to absorb new and difficult concepts. Moreover, observational studies are needed to gain more insight into how specific teaching models affect the retention of relationships and facts—for instance, how inquiry-based learning and its emphasis on lateral thinking can be used as a jumping-off point for more holistic classroom approaches.

Research Conclusion Example and Outline

Let’s revisit the study on the effect of stress on the brain we mentioned before and see what the common structure for a conclusion paragraph looks like, in three steps. Following these simple steps will make it easy for you to wrap everything up in one short paragraph that contains all the essential information: 

One: Short summary of what you did, but integrated into the summary of your findings:

While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study in 25 university students going through mid-term exams show that, surprisingly, one’s attitude to the experienced stress significantly modulates the brain’s response to it. 

Note that you don’t need to repeat any methodological or technical details here—the reader has been presented with all of these before, they have read your results section and the discussion of your results, and even (hopefully!) a discussion of the limitations and strengths of your paper. The only thing you need to remind them of here is the essential outcome of your work. 

Two: Add implications, and don’t forget to specify who this might be relevant for: 

Students could be considered a specific subsample of the general population, but earlier research shows that the effect that exam stress has on their physical and mental health is comparable to the effects of other types of stress on individuals of other ages and occupations. Further research into practical ways of modulating not only one’s mental stress response but potentially also one’s brain activity (e.g., via neurofeedback training) are warranted.

This is a “research implication”, and it is nicely combined with a mention of a potential limitation of the study (the student sample) that turns out not to be a limitation after all (because earlier research suggests we can generalize to other populations). If there already is a lot of research on neurofeedback for stress control, by the way, then this should have been discussed in your discussion section earlier and you wouldn’t say such studies are “warranted” here but rather specify how your findings could inspire specific future experiments or how they should be implemented in existing applications. 

Three: The most important thing is that your conclusion paragraph accurately reflects the content of your paper. Compare it to your research paper title , your research paper abstract , and to your journal submission cover letter , in case you already have one—if these do not all tell the same story, then you need to go back to your paper, start again from the introduction section, and find out where you lost the logical thread. As always, consistency is key.    

Problems to Avoid When Writing a Conclusion 

  • Do not suddenly introduce new information that has never been mentioned before (unless you are writing an essay and opting for an externalizing conclusion, see above). The conclusion section is not where you want to surprise your readers, but the take-home message of what you have already presented.
  • Do not simply copy your abstract, the conclusion section of your abstract, or the first sentence of your introduction, and put it at the end of the discussion section. Even if these parts of your paper cover the same points, they should not be identical.
  • Do not start the conclusion with “In conclusion”. If it has its own section heading, that is redundant, and if it is the last paragraph of the discussion section, it is inelegant and also not really necessary. The reader expects you to wrap your work up in the last paragraph, so you don’t have to announce that. Just look at the above example to see how to start a conclusion in a natural way.
  • Do not forget what your research objectives were and how you initially formulated the statement of the problem in your introduction section. If your story/approach/conclusions changed because of methodological issues or information you were not aware of when you started, then make sure you go back to the beginning and adapt your entire story (not just the ending). 

Consider Receiving Academic Editing Services

When you have arrived at the conclusion of your paper, you might want to head over to Wordvice AI’s AI Writing Assistant to receive a free grammar check for any academic content. 

After drafting, you can also receive English editing and proofreading services , including paper editing services for your journal manuscript. If you need advice on how to write the other parts of your research paper , or on how to make a research paper outline if you are struggling with putting everything you did together, then head over to the Wordvice academic resources pages , where we have a lot more articles and videos for you.

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Writing a research paper is tedious, and after all that work, you’d think the conclusion would be the easy part. In reality, this is often one of the most difficult sections of a research paper to write, since you have to neatly tie up pages and pages of research in a short amount of time.

To help you with this, we’ve put together some instructions and tips on how to write a research paper conclusion. We’ll also talk about what conclusions are, why they’re important, and different ways you can format them.

Key Takeaways

Research paper conclusions serve to close the argument the introduction opened and restate the main points of the research paper.

There are three research paper conclusion formats: summarization, reflective, and projective.

Your research paper conclusion should be concise, straightforward, and accurate.

How to Write a Conclusion for a Research Paper

How To Write A Research Paper Conclusion

6 tips for writing a research paper conclusion, different formats of research paper conclusions, what is the conclusion of a research paper, why is writing a conclusion important for a research paper, research paper conclusion faq.

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Many students understand that the conclusion is a crucial part of their research paper, but they don’t know how to go about writing one.

Follow the steps below for how to write a research paper conclusion.

Open With The Research Topic. To begin a conclusion paragraph, use the first sentence to reiterate the comprehensive subject matter that your paper covered. Since this is just a sentence-long retelling of your research topic and why it’s important, it doesn’t have to be specific, but it does need clarity.

Dragonflies are a magnificently complex insect whose advanced physical mechanics and vast species differences make them a notable study in the scientific community.

Focus On Your Specific Thesis. Every research paper focuses on targetted intricacies within a larger topic. Now that the more extensive topic of the research paper has been mentioned, the next sentence or two highlights the specific thesis presented.

Don’t merely copy and paste the introduction of your thesis from the first paragraph. Restate it in different words that illicit a more in-depth understanding from the reader .

The overall characteristics found only within the Odonata family unites the dragonfly under a singular title. All species of dragonfly faced the same path towards the modern structure known today, and therefore, they are all similar in one way or another. However, there are also significant differences apparent to the naked eye between a species that shares so much of the same structure.

Summarize And Connect Main Points. Throughout a research paper, the writer presents points to support the initial thesis claim. Very briefly summarize and tie together these points in a way that supports your thesis. This is the place to restate your research findings.

By examining the striped meadowhawk and migrant hawker dragonflies, it is shown that habitat governs many aspects pertaining to that specific species’ lifestyle. It is also proven that color and patterns perceived on this insect serve a greater purpose of individualizing and distinguishing between these two species.

Bring It All Together. It sounds redundant to say you need to conclude your conclusion, but that’s the final step. You’ve done the mini recap of your research paper through the beginning sentences of your essay. Close the conclusion by making a final encouragement for an action, idea, or fact.

The dragonfly is a unique insect with uniting factors and specialization. However, the most attributed aspect to this insect as a whole is the enormity of their differences. The evolved genetic features attributed to various species of dragonflies both individualize them and apply unification to the insect as a whole.

Consider What Conclusion Format To Use Carefully. The way you structure a conclusion has a massive effect on how impactful it will be to a reader.

Some types of writing can work well with a variety of conclusion formats, but others will confuse a paper’s message. For example, using a reflective style conclusion on a scientific research paper comes across as too opinion-based for a topic that’s shrouded in measurable fact.

Don’t Make It Too Complex. It’s best to use plain language when summarizing the information presented in a research paper or making a claim. Many students are tempted to use impressive wording and complex writing in a research paper conclusion to present themselves as experts in the subject , but it only gives the reader a headache.

Conclusions Should Be Concise . Research papers give the writer pages of leeway to make all the drawn-out points that they need, but conclusions don’t offer as much room. An essay’s conclusion needs to be short by definition because it’s merely a last takeaway for the reader. A research paper conclusion is a final paragraph, not the entire page .

Double Check Your Information. There’s nothing worse for a research paper’s validity than confidently making a claim in the conclusion that turns out to be false. It’s fundamental that all the facts and information your detail in a research paper are backed up with credible sources listed neatly on the works cited page.

Empathize With The Reader. Whether you’re submitting a research paper for an introductory university class or publishing a scholarly journal, you still need to keep the reader in mind when writing a conclusion. Think about who you’re communicating with through your research paper and what you’re hoping to accomplish with it.

Do Research . One way to fix the problem if you’re unsure of what makes an essay conclusion compelling is researching the topic. Reading articles (like this one) is helpful because they give you a clear demonstration of how to create a conclusion, but applying this structure to your own work can be difficult. A case of easier said than done.

Based on the goal or subject of your research paper, the structure of your conclusion changes. Pick a type of conclusion that will strengthen the point of your essay. Below are examples of different formats to use when writing research paper conclusions.

Summarization. The summarization conclusion is most commonly used for research papers that are presenting a series of concrete facts.

It’s the form of conclusion that most people are familiar with. Using the summary technique requires a succinct compiling of the most critical points you’ve made in an essay.

Summarization Conclusion Formatting Works Best For:

Solution-Based Research

Persuasive Writing

History and Science Studies

Structuring An Argument

Reflective. A conclusion that uses a reflective structure takes the information outlined in the research paper to arrive at a grander insight about the topic at hand. This type of conclusion is popular when you’re attempting to change the reader’s viewpoint with a paper.

Reflective Conclusion Formatting Works Best For:

Persuasive Essays

English and Political Studies

Projective. When using a projective conclusion, the writer applies their work presented earlier in the thesis to eventual outcomes that can arise. It is called a projective conclusion because it is more results-based than summarizing facts or establishing an overarching lesson.

Projective Conclusion Formatting Works Best For:

Research Paper

Expository Essay

Narrative Works (Sometimes)

The conclusion of a research paper ties together all the prior information you’ve covered. It leaves the reader with a final thought about the research paper and the message it’s trying to convey.

Unlike the body paragraphs of a research paper, which aim at specificity and focus on developing a single concept or piece of information, conclusions are broader. The goal is to gloss over what’s already been stated earlier in the essay to solidify it with the reader.

The conclusion also serves a different purpose than the introduction . An introductory paragraph is for establishing what the reader will be learning more about. It opens the metaphorical door towards understanding a research endeavor or topic. The conclusion closes the argument that the introductory paragraph opens.

Including a conclusion is an important part of writing a research paper because it creates an organized summarization of information and outlines inferences about the subject studied. It provides an additional layer of clarity in a short written work.

Research papers are often lengthy and dull, so it’s easy for a reader’s attention to stray. A conclusion brings the reader back and offers them the most critical takeaways from the paper.

How long should a good conclusion be?

A good conclusion should be one paragraph or three to five sentences long. Your research paper conclusion should be concise, which means you don’t need to take up a whole page for just your conclusion. Instead, try to stick to about one paragraph in length.

What are the general rules in crafting conclusions in your research paper?

The general rules for crafting conclusions for your research paper include:

Choose the right conclusion format.

Keep it simple.

Be concise.

Be accurate.

Keep the reader’s needs (or requirements) in mind.

Remind the reader of your thesis.

Summarize and connect main points.

End with a concluding sentence.

What is a better way to say, “In conclusion”?

A better way to say, “In conclusion,” is “Therefore,” “Finally,” or “Lastly.” Other good words include, “As expressed” or “As a result.” You can also simply launch into your concluding paragraph if a transition isn’t needed.

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Sky Ariella is a professional freelance writer, originally from New York. She has been featured on websites and online magazines covering topics in career, travel, and lifestyle. She received her BA in psychology from Hunter College.

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  • Published: 09 February 2024

Key influences on university students’ physical activity: a systematic review using the Theoretical Domains Framework and the COM-B model of human behaviour

  • Catherine E. B. Brown 1 ,
  • Karyn Richardson 1 ,
  • Bengianni Halil-Pizzirani 1 ,
  • Lou Atkins 2 ,
  • Murat Yücel 3   na1 &
  • Rebecca A. Segrave 1   na1  

BMC Public Health volume  24 , Article number:  418 ( 2024 ) Cite this article

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Metrics details

Physical activity is important for all aspects of health, yet most university students are not active enough to reap these benefits. Understanding the factors that influence physical activity in the context of behaviour change theory is valuable to inform the development of effective evidence-based interventions to increase university students’ physical activity. The current systematic review a) identified barriers and facilitators to university students’ physical activity, b) mapped these factors to the Theoretical Domains Framework (TDF) and COM-B model, and c) ranked the relative importance of TDF domains.

Data synthesis included qualitative, quantitative, and mixed-methods research published between 01.01.2010—15.03.2023. Four databases (MEDLINE, PsycINFO, SPORTDiscus, and Scopus) were searched to identify publications on the barriers/facilitators to university students' physical activity. Data regarding study design and key findings (i.e., participant quotes, qualitative theme descriptions, and survey results) were extracted. Framework analysis was used to code barriers/facilitators to the TDF and COM-B model. Within each TDF domain, thematic analysis was used to group similar barriers/facilitators into descriptive theme labels. TDF domains were ranked by relative importance based on frequency, elaboration, and evidence of mixed barriers/facilitators.

Thirty-nine studies involving 17,771 participants met the inclusion criteria. Fifty-six barriers and facilitators mapping to twelve TDF domains and the COM-B model were identified as relevant to students’ physical activity. Three TDF domains, environmental context and resources (e.g., time constraints), social influences (e.g., exercising with others), and goals (e.g., prioritisation of physical activity) were judged to be of greatest relative importance (identified in > 50% of studies). TDF domains of lower relative importance were intentions, reinforcement, emotion, beliefs about consequences, knowledge, physical skills, beliefs about capabilities, cognitive and interpersonal skills, social/professional role and identity, and behavioural regulation. No barriers/facilitators relating to the TDF domains of memory, attention and decision process, or optimism were identified.


The current findings provide a foundation to enhance the development of theory and evidence informed interventions to support university students’ engagement in physical activity. Interventions that include a focus on the TDF domains 'environmental context and resources,' 'social influences,' and 'goals,' hold particular promise for promoting active student lifestyles.

Trial registration

Prospero ID—CRD42021242170.

Peer Review reports

Physical activity (PA) has a powerful positive impact on all aspects of health. Regular PA can prevent and treat noncommunicable diseases [ 1 , 2 ], build resilience against the development of mental illness [ 3 ], and attenuate cognitive decline [ 4 ]. Given these pervasive health benefits, increasing participation in PA is recognised as a global priority by international public health organisations. Indeed, a core aspect of the World Health Organisation’s action plan for a “healthier world” is to achieve a 15% reduction in the global prevalence of physical inactivity by 2030 [ 5 ].

Despite international efforts to reduce physical inactivity, university students frequently do not meet the recommended level of PA required to attain its health benefits. Approximately 40–50% of university students are physically inactive [ 6 ], many of whom attribute their inactivity to unique challenges associated with university life. For many students, the transition to university coincides with new academic, social, financial, and personal responsibilities [ 7 ], disrupting established routines and imposing additional barriers to the initiation or maintenance of healthy lifestyle habits such as regular PA [ 8 ]. Students’ PA tends to decline further during periods of high stress and academic pressure, such as exams and assignment deadlines [ 9 ]. This pattern has been observed across diverse university populations and cultural contexts [ 10 , 11 , 12 ], highlighting the importance of understanding the factors that contribute to physical inactivity among this cohort globally.

Understanding the barriers and facilitators to PA in the context of the university setting is an important step in developing effective, targeted interventions to promote active lifestyles among university students. A recently published systematic review found that lack of time, motivation, access to places to practice PA, and financial resources were primary barriers to PA for undergraduate university students [ 13 ]. A corresponding and complementary synthesis of the facilitators of PA, however, has not yet been conducted. Such a synthesis would be valuable in enabling a comprehensive understanding of the factors that influence students' PA and identifying facilitators that could be leveraged in intervention design. Furthermore, applying theoretical frameworks to understand barriers and facilitators to PA can guide the development of theory-informed, evidence-based interventions for university students that purposely and effectively target factors that influence their participation in PA.

The Theoretical Domains Framework (TDF) [ 14 , 15 , 16 ] and the COM-B model of behaviour [ 17 ] are two robust, gold-standard frameworks frequently used to examine the determinants of human behaviour. The TDF is an integrated framework of 14 theoretical domains (see Additional file 1 for domains, definitions, and constructs) which provide a comprehensive understanding of the key factors driving behaviour. The TDF was developed through expert consensus, synthesising 33 psychological theories (such as social cognitive theory [ 18 , 19 ] and the theory of planned behaviour [ 20 , 21 ] and 128 theoretical constructs (such as ‘competence’, ‘goal priority’, etc.) across disciplines identified as most relevant to the implementation of behaviour change interventions. Identifying the relative importance of theoretical domains allows intervention designers to triage which behaviour change strategies should be prioritised in intervention development [ 22 , 23 ]. The TDF has been widely applied by researchers and practitioners to systematically identify which theoretical domains are most relevant for understanding health behaviour change and policy implementation across a range of contexts, including education [ 24 ], healthcare [ 25 ], and workplace environments [ 26 ].

The 14 TDF domains map onto the COM-B model (Fig.  1 ), which is a broader framework for understanding behaviour and provides a direct link to intervention development frameworks. The COM-B model posits that no behaviour will occur without sufficient capability, opportunity, and motivation. Where any of these are lacking, they can be strategically targeted to support increased engagement in a desired behaviour, including participation in PA. Within the COM-B model, capability can be psychological (e.g., knowledge to engage in the necessary processes) or physical (e.g., physical skills); opportunity can be social (e.g., interpersonal influences) or physical (e.g., environmental resources); and motivation can be automatic (e.g., emotional reactions, habits) or reflective (e.g., intentions, beliefs). The COM-B model was developed through a process of theoretical analysis, empirical evidence, and expert consensus as a central part of a broader framework for developing behaviour change interventions known as the Behaviour Change Wheel (BCW) [ 17 ].

figure 1

The TDF domains linked to the COM-B model subcomponents

Note. Reproduced from Atkins, L., Francis, J., Islam, R., et al. (2017) A guide to using the Theoretical Domains Framework of behaviour change to investigate implementation problems. Implementation Science 12, 77.

Using the TDF and COM-B model to understand the barriers and facilitators to university students’ participation in PA is valuable to inform the development of effective evidence-based interventions that are tailored to address the most influential determinants of behaviour change. As such, this systematic review aimed to: a) identify barriers and facilitators to university students’ participation in PA; b) map these factors using the TDF and COM-B model; and c) determine the relative importance of each TDF domain.

Study design

The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [ 27 ]. The review protocol was registered on PROSPERO (CRD42021242170).

Search strategy

Search terms and parameters were developed in collaboration with a Monash University librarian with expertise in systematic review methodology. The following databases were searched on 15.03.2023 to identify relevant literature: MEDLINE, PsycINFO, and SPORTDiscus. Key articles were also selected for citation searching via Scopus. In consultation with a librarian, these databases were selected due to their unique scope, relevance, broad coverage, and utility. This process ensured the identified literature aligned with the aim and research topic of our systematic review. A 01.01.2010—15.03.2023 publication period was purposefully specified to account for the significant advancements in digital fitness support and tracking tools within the past decade [ 28 ], All available records were searched using the following combination of concepts in the title or abstract of the article: 1) barriers, facilitators, or intervention, Footnote 1 2) physical activity, 3) university, and 4) students. Each search concept was created by first developing a list of search terms relevant to each concept (e.g., for the ‘physical activity’ concept search terms included ‘physical exercise’, ‘physical fitness’, ‘sports’, ‘inactive’, ‘sedentary’, etc.). To create each concept, search terms were then searched collectively using the operator ‘OR’. Each search concept was then combined into the final search by using the operator ‘AND’. Search terms related to concepts 1, 2 and 3 included indexed terms unique and relevant to each database (i.e., Medical Subject Heading Terms for MEDLINE, Index Terms for PsycINFO, and Thesaurus terms for SPORTDiscus). The search was performed according to Boolean operators (e.g., AND, OR) (see Additional file 2 for the complete search syntax for MEDLINE). Unpublished studies were not sought.

Selection criteria

Articles were included if they: (a) reported university students’ self-reported barriers and/or facilitators to physical activity or exercise Footnote 2 ; (b) were written in English; and (c) were peer-reviewed journal articles. Articles encompassed studies directly investigating barriers and/or facilitators to students’ participation in PA and physical exercise intervention studies, where the latter reported participants’ self-reported barriers and/or facilitators to intervention adherence (see Table  1 below for full criteria).

Study selection

Identified articles were uploaded to EndNote X9 software [ 30 ]. A duplication detection tool was used to detect duplicates, which were then screened for accuracy by CB prior to removal. The remaining articles were uploaded to Covidence to enable blind screening and conflict resolution. Articles were screened at the title and abstract level against the inclusion and exclusion criteria by author CB, and 25% were independently screened by BP. The full text of studies meeting the inclusion criteria was then screened against the same criteria by CB, and 25% were again independently screened by BP. Differences were resolved by an independent author (KR). Inter-rater agreement in screening between CB and BP was high (0.96 for title and abstract screening, 0.83 for full-text screening). The decision to dual-screen 25% of studies was strategically chosen to balance thoroughness with efficiency, ensuring both the validity of the screening criteria and the reliability of the primary screener’s decisions. This approach aligns with the protocols used in similar systematic reviews in the field (e.g., [ 31 , 32 ]).

Data extraction

Key article characteristics were extracted, including the author/s, year of publication, country of origin, participant characteristics (e.g., enrolment status, exercise engagement [if reported]), sample size, research design, methods, and analytical approach. Barriers and facilitators were also extracted for each article and subsequently coded according to the 14 domains of the TDF and six subcomponents of the COM-B model. Quantitative data were only extracted if ≥ 50% of students endorsed a factor as a barrier or facilitator. This cut-off criterion was applied to maintain focus on the most common variables of influence and aligns with other reviews synthesising common barriers and facilitators to behaviour change (e.g., [ 26 , 33 ]).

A coding manual was developed to guide the process of mapping barriers and facilitators to the TDF and COM-B. All articles were independently coded by at least two authors (CB and BS, BP or KR). The first version of the manual was developed a priori, based on established guides for applying the TDF and COM-B model to investigate barriers and facilitators to behaviour [ 14 , 34 ], and updated as needed via regular consultation with a co-author and TDF/COM-B designer LA to ensure the accuracy of the data extraction. Barriers and facilitators were only coded to multiple TDF domains if deemed essential to accurately contextualise the core elements of the barrier/facilitator, and when the data in individual papers was described in sufficient detail to indicate that more than one domain was relevant. For example, if ‘lack of time due to competing priorities’ was reported as a barrier to PA, this encompassed both the ‘environmental context and resources’ (i.e., time) and ‘goals’ (i.e., competing priorities) domains of the TDF. Coding conflicts were resolved via discussion with LA.

Data analysis

The following three-step method was utilised to synthesise quantitative and qualitative data:

Framework analysis [ 35 ] was conducted to deductively code barriers and facilitators onto TDF domains and COM-B subcomponents. This involved identifying barriers and facilitators in each article, extracting and labelling them, and determining their relevance against the definitions of the TDF domains and COM-B subcomponents. This process involved creating tables to assist in the systematic categorisation of barriers and facilitators into relevant TDF domains and COM-B subcomponents.

Within each TDF domain, thematic analysis [ 36 ] was conducted to group similar barriers and facilitators together and inductively generate summary theme labels.

The relative importance of each TDF domain was calculated according to frequency (number of studies), elaboration (number of themes) and the identification of mixed barriers/facilitators regarding whether a theme was a barrier or facilitator within each domain (e.g., if some participants reported that receiving encouragement from their family to exercise was a facilitator, and others reported that lack of encouragement from their family to exercise was a barrier). The rank order was determined first by frequency, then elaboration, and finally by mixed barriers/facilitators.

This methodology follows previous studies using the TDF and COM-B to characterise barriers and facilitators to behaviour change and rank their relative importance [ 22 , 23 ].

Study characteristics

Following the removal of duplicates, 6,152 articles met the search criteria and were screened based on title and abstract. A total of 5,995 articles were excluded because they did not meet the inclusion criteria (see Fig.  2 below for the PRISMA flowchart). After the title and abstract screening, 157 full-text articles were retrieved and assessed for eligibility. One additional article was identified and included following citation searching of selected key articles. Thirty-nine articles met the inclusion criteria (see Additional file 3 for a summary of these studies). Eight studies were conducted in the USA, seven in Canada, three in Germany, two each in Qatar, Spain, the United Arab Emirates, and the United Kingdom, and one each in Australia, Belgium, Columbia, Egypt, Ireland, Japan, Kuwait, Malaysia, New Zealand, Saudi Arabia, South Africa, Sri Lanka, and Uganda.

figure 2

PRISMA flowchart illustrating the article selection process

Relative importance of TDF domains and COM-B components

Twelve of the 14 TDF domains and all six subcomponents of the COM-B model were identified as relevant to university students' PA. The rank order of relative importance of TDF domains and associated COM-B subcomponents are presented in Table  2 . The three most important domains were identified in at least 54% of studies.

Barriers and facilitators to student’s physical activity

Within the TDF domains, 56 total themes were identified, including 26 mixed barriers/facilitators, 18 facilitators and 12 barriers (Table  3 ). The barriers and facilitators identified within each TDF domain are summarised below (with associated COM-B subcomponent presented in parentheses), in order of relative importance:

1. Environmental context and resources (Physical Opportunity) ( n  = 90% studies)

The most frequent barrier to PA across all TDF domains was ‘lack of time’, most often in the context of study demands. Time constraints were exacerbated by long commutes to university, family responsibilities, involvement in co-curricular activities, and employment commitments. Students’ need for ‘easily accessible exercise options, facilities and equipment’ was a recurring theme. PA was deemed inaccessible if exercise facilities and other infrastructure to support PA, such as bike paths and running trails, were situated too far from the university campus or students’ residences, or if fitness classes were scheduled at inconvenient times. ‘Financial costs’ emerged as a theme. The costs associated with accessing exercise facilities, equipment and programs consistently deterred students from engaging in PA. The desire for ‘safe and enjoyable’, ‘weather appropriate’ environments for PA were frequently reported. Participating in outdoor PA in green spaces or near water increased enjoyment, provided the environment felt safe and weather conditions were suitable for PA. Factors related to students’ home, work, and university environment impacted their participation in ‘incidental PA’. Incidental PA was influenced by whether students engaged in domestic house chores, and manual work, and actively commuted to university and between classes on-campus. Students’ ‘access to a variety of physical activities’ and ‘information provision regarding on-campus exercise options’ impacted their PA. Students most often had access to a wide variety of physical activities, however, it could be difficult to access information about what types of activities were available on-campus and how to sign up to participate. The ‘lack of personalised physical activities to cater to individual fitness needs’ was a barrier, particularly for students with low levels of PA who required beginner-oriented programs. Another barrier was the ‘lack of university policy and promotion to encourage PA’, which led students to perceive that there was no obligation to participate in PA and that the university did not value it. ‘Health-concerning behaviours associated with university’, including poor diet, increased alcohol intake and sedentary behaviour, negatively impacted students’ PA. ‘Listening to music while exercising’ was a facilitator.

2. Social influences (Social Opportunity) ( n  = 72% studies)

Within social influences, ‘exercising with others’ emerged as the most frequent theme. Doing so increased students’ accountability, enjoyment and motivation, and helped them to overcome feelings of intimidation when exercising alone. Having a lack of friends to exercise with was a particular concern for students who were new to exercise or infrequently participated in PA. Receiving ‘encouragement from others to be physically active’, such as family members, friends, peers, and fitness instructors, shaped students’ values toward PA and enhanced their motivation and self-efficacy. Students’ family members, friends and teachers discouraged PA if it was not valued, or in favour of other priorities, such as academic commitments. Another recurrent theme was ‘competition or relative comparison to others’. While most students were motivated by competition, a minority felt demotivated if they compared themselves to others with higher PA standards, especially if they failed to achieve similar PA goals. Sociocultural norms influenced barriers/facilitators to PA across different cultures, and between various groups, such as international versus domestic students, and women versus men. Students from Japan and Hawaii viewed PA as an important part of their culture, in contrast to students from the Philippines who described the opposite. Participation in PA enabled international students to integrate with domestic students and learn about the local culture, however cultural segregation was a barrier to participation in university team sports. For female students from some middle-eastern countries, including Saudi Arabia, the UAE and Qatar, cultural norms made it impermissible for women to engage in PA, particularly compared to men. Religion also differentially impacted barriers/facilitators between women and men. Muslim women reported that Islamic practices, such as needing to engage in PA separately from men, be accompanied by a male family member while going outdoors, or dress modestly, posed additional barriers to PA. However, one study reported that Islamic teachings generally encouraged PA for both women and men by emphasising the importance of maintaining good health. Other gender-specific barriers were identified. Women often felt unwelcome or intimidated by men in exercise facilities, partly due to the perception that these facilities were tailored toward “masculine” sports and/or dominated by men. ‘Being stared at while engaging in PA’ was another barrier, impacting both women and students with a disability. A less common facilitator was the influence of both positive and negative ‘exercise role models’. For example, students practiced PA because they aspired to be like someone who was physically active, or because they did not want to be like someone who was not physically active.

3. Goals (Reflective Motivation) ( n  = 54%)

‘Prioritisation of PA compared to other activities’ was the most common theme within goals. Students frequently prioritised other activities, such as study, social activities, or work, over PA. However, those who played team sports or regularly practiced PA were more inclined to prioritise it for its recognised health benefits (i.e., stress management), and its role in enhancing confidence. Additional facilitators included ‘engaging in PA to achieve an external goal’, such as improving one’s appearance, and ‘setting specific PA-related goals’ as a means to enhance accountability.

4. Intentions (Reflective Motivation) ( n  = 44%)

Within intentions, ‘motivation to engage in PA’ was the most common theme. Students most often noted a lack of self-motivation for PA. Less frequent barriers included perceiving PA as an obligatory or necessary "chore", and ‘failing to follow through on intentions to engage in PA’. Conversely, ‘self-discipline to engage in PA’ emerged as a facilitator that assisted students in maintaining a regular PA routine.

5. Reinforcement (Automatic Motivation) ( n  = 38%)

The most frequent facilitator within reinforcement was ‘experiencing the positive effects of PA’ on their health and wellbeing. These included physical health benefits (i.e., maintaining fitness), psychological benefits (i.e., stress reduction), and cognitive health benefits (i.e., enhanced academic performance). Conversely, barriers arose from ‘experiencing discomfort during or after PA’ due to pain, muscle soreness or fatigue. ‘Past and current habits and routines’ was a theme. Students were more likely to participate in PA if they had established regular exercise routines, and that forming these habits at an early age made it easier to maintain them later in life. However, maintaining a regular PA routine was difficult in the context of inflexible university schedules. Students’ ‘sense of accomplishment in relation to PA’ was a theme. Students were less likely to feel a sense of accomplishment after participating in PA if it was not physically challenging. Consistent facilitators were ‘receiving positive feedback from others’ after engaging in PA, such as compliments, and ‘receiving incentives’, such as reducing the cost of gym memberships if students participated in more PA. ‘Experiencing a sense of achievement’ after reaching a PA-related goal or winning a sports match also served as a facilitator.

6. Emotion (Automatic Motivation) ( n  = 38%)

‘Enjoyment’ was the most frequently cited emotional theme. Most students reported that PA was fun and/or associated with positive feelings, however, a minority described PA as unenjoyable, boring, and repetitive. Students’ ‘poor mental health and negative affectivity’ (such as feeling sad, stressed or self-conscious, as well as fear of injury and pain), adversely impacted their motivation to be physically active.

7. Beliefs about consequences (Reflective Motivation) ( n  = 31%)

‘Beliefs about the physical health consequences of PA’ was the most recurrent barrier/facilitator. Most students understood that PA was essential for maintaining good health and preventing illness. However, some students who rarely or never engaged in PA believed they could delay pursuing an active lifestyle until they were older without compromising their health. Participating in PA to ‘maintain or improve one’s physical appearance’ acted as a facilitator. This motivation was most often cited in contexts such as increasing or decreasing weight, changing body shape or enhancing muscle tone. Beliefs about the positive environmental, occupational and psychological impacts of PA also served as facilitators. Students were motivated to participate in PA due to the environmental benefits of using active transport. They also acknowledged the importance of being physically fit for work and believed that being active was beneficial for mental health. ‘Receiving advice to participate in PA from a credible source’, such as a health professional, further facilitated students’ motivation to be active.

8. Knowledge (Psychological Capability) ( n  = 28%)

'Knowledge about the benefits of PA’, encompassing an understanding of the various types of benefits (i.e., physical, mental, or cognitive) and the biological mechanisms by which PA brings about these changes was identified as the most common knowledge theme. Being aware of these benefits positively influenced students’ motivation to be physically active. Conversely, students’ lack of knowledge about the gym environment and the programs available were barriers to PA. Regarding the gym environment, students’ ‘lack of knowledge about how to navigate through the gym, what exercises to do, and how to use exercise equipment’ amplified feelings of intimidation. Likewise, ‘lack of knowledge about the types of exercise programs and activities that were available on-campus, and how to sign up to participate’ were all barriers. A unique theme emerged concerning ‘knowledge about how to adapt physical activities for students with a disability’. Students with a disability described how fitness instructors often had a limited understanding of how to modify activities to enable them to participate. However, students with a disability were able to overcome this barrier if they possessed their own knowledge about how to tailor physical activities to meet their specific needs.

9. Physical skills (Physical Capability) ( n  = 21%)

The most prevalent theme within physical skills was ‘having the physical skills and fitness to participate in PA’. A lack of physical skills was most frequently a hindrance to PA. Additional obstacles to PA included being physically inhibited due to a ‘lack of energy’ or ‘physical injury’.

10. Beliefs about capabilities (Reflective Motivation) ( n  = 18%)

Within beliefs about capabilities, ‘self-efficacy to participate in PA’ was the most recurrent theme. Students who doubted their success in becoming physically active or who lacked confidence in their ability to initiate PA or participate in sport were less motivated to take part. A less frequent facilitator was students’ ‘self-affirmation to participate in PA’, often referring to positive cognitions about one’s own physical abilities.

11. Cognitive and interpersonal skills (Psychological Capability) ( n  = 15%)

‘Time-management’ was the only theme identified within cognitive and interpersonal skills. Students who struggled to manage their time effectively found it difficult to incorporate regular PA into their daily routine.

12. Social/professional role and identity (Reflective Motivation) ( n  = 8%)

The most frequent theme within social/professional role and identity was ‘perceiving PA as a part of one’s self-identity’. Students who engaged regularly in PA often considered it integral to their identity. Conversely, students who perceived they did not align with the aesthetic and superficial stereotypes commonly associated with the fitness industry felt less motivated to be active. A specific facilitator emerged among physiotherapy students, who were motivated to be active due to the emphasis on PA within their profession.

13. Behavioural regulation (Psychological Capability) ( n  = 3%)

Within the domain of behavioural regulation, two facilitators were equally prevalent: ‘self-monitoring of PA’ and ‘feedback on progress towards a PA-related goal’. By keeping track of their step count and receiving feedback on walking goals, students were motivated to exceed the average number of daily steps or achieve their personal PA targets.

14. Memory, attention, and decision process (Psychological Capability); Optimism (Reflective Motivation) ( n  = 0%)

No barriers or facilitators relating to the TDF domains of memory, attention and decision process, or optimism were identified.

This systematic review used the TDF and COM-B model to identify barriers and facilitators to PA among university students and rank the relative importance of each TDF domain. It is the first review to apply these frameworks in the context of increasing university students’ participation in PA. Twelve TDF domains across all six sub-components of the COM-B model were identified. The three most important TDF domains were ‘environmental context and resources’, ‘social influences’, and ‘goals’. The most common barriers and facilitators were ‘lack of time’, ‘easily accessible exercise options, facilities and equipment’, ‘exercising with others’, and ‘prioritisation of PA compared to other activities’.

The most common barrier to PA was perceived lack of time. This is consistent with previous findings among university students [ 13 , 74 ] and across other populations [ 24 ], For students, lack of time was frequently attributed to a combination of competing priorities and underdeveloped time management skills. Students predominantly prioritised study over PA, as performing well at university is a valued goal and there is a common perception that spending time exercising (at the expense of study) will impede their academic success [ 53 , 58 ]. Evidence from cognitive neuroscience research, however, suggests that this is a mistaken belief. In addition to its broad physical and mental health benefits, a growing body of evidence demonstrates regular PA can change the structure and function of the brain.

These changes can, in turn, enhance numerous aspects of cognition, including memory, attention, and processing speed [ 4 , 75 , 76 , 77 ], and buffer the negative impact of stress on cognition [ 78 ], all of which are important for academic success. However, students are typically unaware of the brain and cognitive health benefits of PA and its potential to improve academic performance, particularly compared to the physical health benefits [ 37 , 40 , 64 ]. Interventions that position participating in PA as a conduit for helping, rather than hindering, academic goals could increase the relative importance of PA to students and therefore increase their motivation to regularly engage in it. The impact that interventions of this nature have on students’ PA is yet to be empirically assessed.

Ineffective time management also contributed to students’ perceived lack of time for PA. Students reported tendencies to procrastinate in the face of overwhelming academic workloads, which left limited time for PA [ 53 ]. Additionally, students lacked an understanding of how to organise time for PA around academic timetables, social and family responsibilities, co-curricular activities, and employment commitments [ 9 , 44 , 53 , 59 ]. To address these challenges, efforts to develop students’ time management skills will be useful for enabling students to regularly participate in PA. Goal-setting and action planning are two specific examples of such skills that can be integrated into interventions to help students initiate and maintain a PA routine [ 79 ]. For example, goal-setting could involve setting a daily PA goal, and action planning could involve planning to engage in a particular PA at a particular time on certain days.

While the most common determinants of university students’ PA levels were not influenced by specific demographic characteristics, several barriers disproportionately impacted women and students with a disability. These findings are in keeping with evidence that PA is lower among these equity-deserving groups compared with the general population [ 68 , 80 ]. For women, particularly those from Middle Eastern cultures, restrictions were often tied to religious practices and sociocultural norms that limited their opportunities to engage in PA [ 45 , 48 , 66 ]. Additionally, a substantial number of women felt intimidated or self-conscious when exercising in front of others, especially men [ 48 , 49 ]. They also felt that exercise facilities were more often tailored towards the needs of men, leading to a perception that they were unwelcome in exercise communities [ 45 , 48 ]. Consequently, women expressed a desire for women-only spaces to exercise to help them overcome these gender-specific barriers to PA [ 47 , 48 , 66 ]. Furthermore, students with a disability faced physical accessibility barriers and perceived stigmatisation that deterred them from PA [ 50 , 52 ]. The lack of accessible exercise facilities and suitable equipment, programs, and education regarding how to adapt physical activities to accommodate their needs limited their opportunity and ability to participate [ 52 ]. Moreover, students with a disability felt stigmatised by others for not fitting into public perceptions of ‘normality’ or the aesthetic values and beauty standards often portrayed by the fitness industry [ 50 ]. These barriers for both equity-deserving groups of students are deeply rooted in historical stereotypes that have traditionally excluded women and people with a disability from engaging in various types of PA [ 81 , 82 ]. Despite growing awareness of these issues, PA inequalities persist due to narrow sociocultural norms, and a lack of diverse representation and inclusion in the fitness industry and associated marketing campaigns [ 83 , 84 ]. A concerted effort to address PA inequalities across the university sector and fitness industry more broadly is needed. One approach for achieving this is to develop interventions that are tailored to the unique needs of equity-deserving groups, emphasise inclusivity, diversity, and empowerment, and feature women and people with a disability being active.

The “This Girl Can” [ 85 ] and “Everyone Can” [ 86 ] multimedia campaigns are two examples of health behaviour interventions that were co-developed with key stakeholders (i.e., women and people with a disability, respectively) to tackle PA inequalities. The “This Girl Can” campaign has reached over 3 million women and girls, projecting inclusive and positive messages that aim to empower them to be physically active. Following the widespread reach of the “This Girl Can” campaign, the “Everybody Can” campaign was launched to support the inclusion of people with a disability in the PA sector. Although not tailored for university students, these campaigns provide a useful example for developing interventions that are specifically designed to address key barriers preventing women and people with a disability from participating in PA.

Across the tertiary education sector globally, efforts to elevate opportunities and motivation to include PA as a core part of the student experience will be beneficial for promoting students’ PA at scale. Two intervention approaches that can be implemented to facilitate such an endeavour are environmental restructuring and enablement [ 17 ]. These intervention approaches should involve the provision of accessible low-cost exercise options, facilities, and programs, integrating PA into the university curriculum, and mobilising student and staff leadership to encourage students’ participation in PA [ 9 ]. Although there is evidence that these approaches can be effective in promoting sustained PA throughout students’ university years and beyond [ 87 ], implementation measures such as these are complex. Implementation requires aligning student activity levels with broader university goals and is further complicated by having to compete with other funding priorities and resource allocations. Notably, due to the negative impact of the COVID-19 pandemic on university students’ physical and mental health [ 88 , 89 ], the post-pandemic era has seen many universities prioritise enhancing student health and wellbeing alongside more traditional strategic goals like academic excellence and workforce readiness. Despite the potential for PA to be used as a vehicle for supporting these strategic goals there is an absence of data on the extent to which this is occurring in the university sector. The limited evidence in this area suggests that some universities have made efforts to support students’ mental health by referring students who access on-campus counselling services to PA programs [ 90 ]. However, the uptake and efficacy of such initiatives is rarely assessed, and even less is known about whether PA is being used to support other strategic goals, such as academic success. Therefore, while the potential is there for the university sector to use PA to support students’ mental health and academic performance, to be successful this needs to become a strategic university priority. Given that these strategic priorities are set at the senior leadership level, engaging senior university staff in intervention design and promotion efforts is important to enhance the value of PA in the tertiary education sector.

Implications for intervention development

The current findings provide a high-level synthesis of the most common barriers and facilitators to university students’ physical activity. These findings can be leveraged with behavioural intervention development tools and frameworks (e.g., the BCW [ 17 ], Obesity-Related Behavioural Intervention Trials model [ 91 ], Intervention Mapping [ 92 ], and the Medical Research Council guidelines for developing complex interventions [ 93 , 94 ]) to develop evidence-based interventions and policies to promote PA. Given that the TDF and COM-B model are directly linked to the BCW framework, applying this process may be particularly useful to translate the current findings into an intervention.

Additionally, current findings can be triangulated with data directly collected from key stakeholders to assist in the development of context-specific interventions. Best practice principles for developing behavioural interventions recommend this approach to ensure a deep understanding of the barriers and facilitators that need to be targeted to increase the likelihood of behaviour change [ 17 ]. Consulting stakeholders directly (i.e., university students and staff) to understand their perspectives on the barriers and facilitators to students’ PA also enables an intervention to be appropriately tailored to the target population’s needs and implementation setting. Studies continue to demonstrate the effectiveness of this approach, especially when framed within the context of frameworks directly linked to intervention development frameworks, such as the TDF [ 95 ].

Strengths and limitations

The findings of this review should be considered with respect to its methodological strengths and limitations. The credibility and reliability of the research findings are supported by a systematic approach to screening and analysing the empirical data, along with the use of gold-standard behavioural science frameworks to classify barriers and facilitators to PA. The inclusion of qualitative, quantitative, and mixed-methods studies of both barriers and facilitators to students’ PA allowed for a comprehensive understanding of the factors that influence students’ PA that have not previously been captured.

While the present review elucidates students’ own perspectives of the factors that influence their activity levels, other stakeholders such as university staff, will also influence the adoption, operationalisation, and scale of PA interventions in a university setting. It will be important for future research to explore factors that influence university decision-makers in these roles to inform large-scale strategies for promoting students' PA.

Additionally, only one study included in the review used the TDF to explore barriers and facilitators to PA [ 47 ]. Therefore, it is possible that certain TDF domains may not have been identified because students were not asked relevant questions to assess the influence of those domains on their PA. For instance, domains such as ‘memory, attention, and decision process’, and ‘optimism’ are likely to play a role in understanding the barriers and facilitators to PA despite not being identified in this review.

Moreover, quantitative data were only extracted if ≥ 50% of students endorsed the factor as a barrier or facilitator to PA. This threshold was purposefully applied to maintain a focus on the TDF domains most universally relevant to the broad student population in the context of understanding their barriers and facilitators to PA. It is possible that less frequently reported barriers and facilitators, which may not be as prominently featured in the results, could be relevant to specific groups of students, such as those identified as equity-deserving.

Lastly, a quality appraisal of the included studies was not undertaken. This decision was informed by the aim of the review, which was to describe and synthesise the literature to subsequently map data to the TDF and COM-B rather than assess the effectiveness of interventions or determine the strength of evidence. However, this decision, combined with dual screening 25% of the studies and excluding unpublished studies and grey literature, may introduce sources of error and bias, which should be considered when interpreting the results presented.

PA is an effective, scalable, and empowering means of enhancing physical, mental, and cognitive health. This approach could help students reach their academic potential and cope with the many stressors that accompany student life, in addition to setting a strong foundation for healthy exercise habits for a lifetime. As such, understanding the barriers and facilitators to an active student lifestyle is beneficial. This systematic review applied the TDF and COM-B model to identify and map students’ barriers and facilitators to PA and, in doing so, provides a pragmatic, theory-informed, and evidence-based foundation for designing future context-specific PA interventions. The findings from this review highlight the importance of developing PA interventions that focus on the TDF domains ‘environmental context and resources’, ‘social influences’, and ‘goals’, for which intervention approaches could involve environmental restructuring, education, and enablement. If successful, such strategies could make a significant contribution to improving the overall health and academic performance of university students.

Availability of data and materials

The review protocol is available on PROSPERO. The datasets used and/or analysed during the current study and materials used are available from the corresponding author on reasonable request.

The term ‘intervention’ was included to identify student barriers and facilitators to engaging in implemented physical activity interventions.

Physical exercise is defined as “a subset of physical activity that is planned, structured, and repetitive”, and purposefully focused on the improvement or maintenance of physical fitness, whereas physical activity is defined as “any bodily movement produced by skeletal muscles that results in energy expenditure” [ 96 ].


Behaviour Change Wheel

Capability, Opportunity, Model-Behaviour

  • Physical activity

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

International Prospective Register of Systematic Reviews

Theoretical Domains Framework

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The authors extend their gratitude to the funder, the nib foundation, for its financial support, which was instrumental in facilitating this research. We are also indebted to the Wilson Foundation and the David Winston Turner Endowment Fund for their generous philanthropic contributions, which have supported the BrainPark research team and facility where this research was conducted. Special thanks are owed to the library staff at Monash University for their expertise in conducting systematic reviews, which helped inform the selection of databases and the development of the search strategy.

This research was supported by nib foundation. The nib foundation had no role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript. The views expressed are those of the authors and not necessarily those of the nib foundation.

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Catherine E. B. Brown, Karyn Richardson, Bengianni Halil-Pizzirani & Rebecca A. Segrave

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CB, KR, BP, LA and RS developed the review protocol. CB and BP conducted the search and screened articles, and KR resolved conflicts. CB, KR, BP, LA and RS extracted the barriers and facilitators, mapped barriers and facilitators to the TDF and COM-B model, and interpreted the results. CB drafted the paper. All authors read, revised, and approved the submitted version.

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Translational research on drug development and biomarker discovery for hepatocellular carcinoma

  • Valerie Chew 1 , 2 ,
  • Chien-Huai Chuang 3 &
  • Chiun Hsu   ORCID: 3 , 4 , 5  

Journal of Biomedical Science volume  31 , Article number:  22 ( 2024 ) Cite this article

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Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist in this field because of the limited availability of human tumor samples from surgery, the lack of homogenous oncogenic driver mutations, and the paucity of adequate experimental models. In this review, we provide insights into these challenges and review recent advancements, with a particular focus on the two main agents currently used as mainstream therapies for HCC: anti-angiogenic agents and immunotherapy. First, we examine the pre-clinical and clinical studies to highlight the challenges of determining the optimal therapeutic combinations with biologically effective dosage for HCC. Second, we discuss biomarker studies focusing on anti-PD1/anti-PD-L1-based combination therapy. Finally, we discuss the progress made in our collective understanding of tumor immunology and in multi-omics analysis technology, which enhance our understanding of the mechanisms underlying immunotherapy, characterize different patient subgroups, and facilitate the development of novel combination approaches to improve treatment efficacy. In summary, this review provides a comprehensive overview of efforts in translational research aiming at advancing our understanding of and improving the treatment of HCC.


The development of new oncology drugs for unresectable HCC has been hindered by limited accessibility to early-phase clinical trials [ 1 ] as well as concerns of adverse events associated with chronic liver diseases or loco-regional therapy [ 2 , 3 ]. Despite these challenges, the introduction of new treatment regimens, including multi-kinase inhibitors (MKIs), immune checkpoint inhibitors (ICI), and their combinations, has not only expanded the treatment options available for patients with advanced-stage HCC but also introduced new prospects of multi-modality treatments for patients with earlier stage diseases [ 4 , 5 ].

Anti-PD1/ anti-PD-L1 ICI-based combination therapy is regarded as the most noteworthy breakthrough in systemic therapy for unresectable HCC. Although findings from recent, pivotal phase III randomized clinical trials play key roles in shaping the future development of novel systemic therapy [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], translational research aiming at elucidating antitumor mechanisms and characterizing patient subgroups who are most likely to benefit from specific treatments is also essential. In this review, we explore the progress of translational research on drug development for HCC treatment from three distinct perspectives, namely, the reader, the interpreter, and the creator, to illustrate how translational research may aid in advancing the understanding and improving the treatment of HCC. As outlined by Dr. Bijay Kumar Das, an Indian literature critic, “A translator is a reader, an interpreter and a creator all in one”. Researchers must be aware of the available literature on HCC treatment and drug development (as readers), capable of analyzing and understanding the complex clinical and pre-clinical data (as interpreters), and, ideally, able to use this knowledge and understanding to design new experiments, develop new drugs, and ultimately advance the field of HCC treatment (as creators).

In this review we focus on the aspects of drug development and biomarker discovery for the 2 major classes of agents that are currently the mainstream therapies for HCC, namely anti-angiogenic agents and ICIs. As readers, we examine how translational research is involved in the development of new drugs for HCC. We also reviewed the preclinical studies focusing on the immunomodulatory effects of anti-angiogenic agents for HCC, highlighting the potential benefits and challenges of using in vivo and in vitro models. As interpreters, we review the correlative biomarker studies from randomized trials of anti-PD1/ anti-PD-L1-based therapy and single-arm cohort studies. We also discuss the benefits and challenges of developing tissue- and blood-based predictive biomarkers and the confounding effects exerted by the underlying etiologies of liver diseases. As creators, we discussed recent advancements in the multi-omics analyses of the HCC micro-environment. Specifically, we focus on advancements in computational biology, which enhance our collective understanding of the complex interactions of immune cells in the tumor microenvironment (TME), and on the implications of these advancements for both efficacy and adverse events of immunotherapy. We also emphasize the need for developing novel pre-clinical models to support mechanistic exploration and biomarker identification. In summary, translational research is a complex and multifaceted process that requires researchers to be readers, interpreters, and creators.

Readers: lessons learned from translational research on anti-angiogenic therapy for HCC

Traditionally, translational research aimed at developing new drugs for HCC has had 2 primary objectives: establishing reliable predictive biomarkers to develop tailored treatment options for specific patient populations and understanding the underlying mechanisms of the new drugs. Nevertheless, achieving these objectives has been challenging for HCC. Clinical diagnosis of HCC, based on clinical and imaging characteristics rather than histological proof, is standard for patients with established risk factors (cirrhosis, chronic viral hepatitis) [ 16 ]. In addition, phase III randomized trials of systemic therapy for unresectable HCC have often not required a histological diagnosis, thereby resulting in a lack of adequate tumor samples for correlative biomarker analysis. Moreover, almost all of the molecular aberrations found in HCC, which have been primarily identified in studies using tumor samples obtained from patients who underwent surgery, are not typical drivers of the carcinogenesis process and are undruggable through either monoclonal antibodies or small molecule inhibitors [ 17 ]. Although molecular classifications of HCC based on genetic or epigenetic features of the tumors have been proposed to predict clinical outcome, they may not help patient categorization for the development of specific targeted therapy [ 18 , 19 ].

Anti-angiogenesis: a plausible yet elusive drug target

Generally, current targeted agents used for HCC treatment primarily exert their anticancer effects through the inhibition of angiogenesis. Although extensive clinical and pre-clinical studies have been conducted, no reliable set of predictive biomarkers has been established for identifying patients who may benefit from antiangiogenic therapy. In addition, no reliable pharmacodynamic markers have been identified to monitor the extent of angiogenesis inhibition and to determine the correlation between anti-angiogenic effects and clinical efficacy. The difficulty of preclinical experimental models to recapitulate the clinical features of HCC emerging from an inflammatory or cirrhotic background further widens the gap between preclinical mechanistic research and clinical application [ 20 , 21 ].

In terms of the development of the anti- vascular endothelial growth factor (anti-VEGF) antibodies, early studies of bevacizumab in murine models suggested that doses of 2.5 mg/kg twice weekly or higher may achieve adequate plasma concentrations and anti-angiogenic effects [ 22 ]. Multiple randomized phase 2 and 3 trials have examined the dose–response effects of bevacizumab, either as single-agent therapy or in combination with chemotherapy, in different types of cancer. In these trials, higher doses of bevacizumab were associated with a trend of better treatment benefit, in terms of superior objective response rate or survival, and higher risks of adverse events, including hypertension, proteinuria and vascular events [ 23 , 24 , 25 , 26 ]. Since most of the adverse events were generally well tolerated by the patients, a high dosage of bevacizumab (5.0 mg/kg/ week) was eventually used in almost all subsequent clinical trials to develop new combination regimens. Overall, these findings underscore the limitations of pre-clinical models for dose determination in real-world clinical trials.

Pharmacodynamic biomarkers for anti-angiogenic therapy, including functional imaging, immunohistochemistry, and levels of circulating cytokines or angiogenic progenitor cells, have been widely tested but none of them have achieved the reproducibility and robustness required as a companion diagnostic in clinical practice [ 27 , 28 ]. For example, in developing the MKI regorafenib, which inhibits VEGF receptor (VEGFR), biomarker experiments, including DCE-MRI functional imaging and circulating VEGFR, indicated that daily regorafenib dosage of 120 mg or higher was necessary to elicit anti-angiogenic effects [ 29 ]. This finding laid the foundation for subsequent clinical trials on HCC and other types of cancer, leading to the current recommended dosage of 160 mg per day, 3-week on and 1-week off. However, this dosage was not well tolerated by most patients. A dose-escalation strategy for regorafenib, starting from 80 mg per day (half of the recommended dose of 160 mg per day), with incremental adjustments depending on patient tolerance until a median daily dosage of 100 mg to 120 mg was reached, has been proposed to achieve similar progression-free survival to that of patients who received the standard-dosage of regorafenib [ 30 ].

The aforementioned challenges are also present in the development of other anti-angiogenic strategies, such as in the modulation of pericyte function. Pericytes play a key role in the stabilization and maturation of vascular sprouts, a process that involves multiple signalling pathways, including the VEGF, platelet-derived growth factor, and angiopoietin/ Tie-2 pathways [ 31 , 32 ]. Translational research platforms to characterize the interaction among multiple relevant mechanisms and to minimize the gaps between pre-clinical evidence and clinical efficacy/ safety are urgently need.

Complex interaction between anti-angiogenetic agents and ICIs

Mechanistic exploration became much more complicated when researchers attempted to address the immune modulatory effects of anti-angiogenic therapy [ 33 ]. Pre-clinical studies revealed that VEGF-targeting therapy can activate antitumor immunity in many aspects, including increasing antigen presentation, activating effector T cells, and counteracting immune suppressor cells in the TME. In addition to VEGF-targeting, tumor angiogenesis can also be indirectly modulated by targeting various immune cells (e.g., tumor-associated macrophages, TAMs) or stromal cells (e.g., pericytes) in the TME. Specific targeting agents and epigenetic-modifying agents are under development to modulate these cells [ 34 , 35 , 36 ]. Given that many plausible targets are available, developing predictive biomarkers for patient selection and pharmacodynamic monitoring has become more challenging.

Hypoxia in the TME plays a key role in the immunomodulatory effects of anti-angiogenic agents. Although HCC is typically a hypervascular tumor, the high interstitial pressure resulting from its aberrant vasculature may paradoxically induce hypoxia and immune suppression in the TME [ 37 , 38 ]. This hypoxia-induced immune suppression involves complex interactions among different immune cells, the stroma, and the cytokine network in the TME [ 39 , 40 , 41 , 42 ]. Therefore, to improve anti-tumor immunity, multiple agents targeting tumor-associated hypoxia have been studied [ 43 , 44 ]. According to the theory of vascular normalization in anti-angiogenic therapy, using excessively high doses of anti-angiogenic agents may induce hypoxia, acidosis and immune suppression in the TME, whereas using low-doses of anti-angiogenic therapy may enhance antigen presentation and improve T cell trafficking and function [ 38 ]. Pre-clinical studies have also indicated that using lower doses of anti-angiogenic MKI may induce vascular normalization, reduce hypoxia, and improve antitumor immunity, whereas using higher doses of anti-angiogenic MKIs may paradoxically increase hypoxia and promote immune suppression [ 45 ].

Understanding the biologically effective dosage of targeted agents and their relevant antitumor mechanisms is essential for developing optimal anti-angiogenic regimens. In our pre-clinical studies on regorafenib, we used regorafenib at a dosage of 5 mg/kg/day in animal models to mimic the half daily recommended dose of regorafenib (i.e., 80 mg per day) in human, in accordance with the aforementioned pharmacokinetic study. We found that this low-dose of regorafenib was associated with enhanced interferon-gamma response, M1 macrophage polarization, and antitumor immunity, independent of its anti-angiogenic effects. Regorafenib inhibits the p38 kinase/ Creb1/Klf4 signaling pathway in macrophages, which may explain its macrophage-polarizing effects [ 46 ]. According to Shigeta et al. (2020), regorafenib at a dosage of 10 mg/kg/day in mouse liver cancer models may result in optimal vascular normalization and increased T-cell infiltration in the TME. Regorafenib may also increase the expression of CXCL10 by HCC cells and the intratumoral infiltration of CD8 + CXCR3 + T cells through the inhibition of STAT3 activity. These two mechanisms may account for the antitumor synergy observed between regorafenib and anti-PD1 therapy [ 47 ]. Overall, these studies have demonstrated how pre-clinical research can elucidate the optimal biologically effective dosage of targeted agents and their mechanisms of action.

In conclusion, the challenges and complexity in drug development and biomarker discovery are significant and must be addressed through reliable pre-clinical studies and solid mechanistic understanding. Overcoming these challenges ca aid in achieve actual progress in the clinical management of HCC, an unmet need that demands urgent attention.

Interpreters: biomarker studies for the prediction of treatment efficacy and mechanistic exploration

Biomarkers are used clinically in risk stratification, early detection, diagnosis, prognosis, and treatment response prediction. Clinical parameters such as tumor size, tumor number, and liver functional reserves are incorporated in major HCC practice guidelines to recommend the choice of liver-directed therapy, such as chemo-embolization [ 4 , 48 , 49 , 50 ]. For patients who require systemic therapy, no reliable set of biomarkers is yet validated for currently available treatment options. Treatment recommendations are typically based on the clinical and laboratory parameters defined in the pivotal clinical trials and on the safety concerns of specific agents and patient preferences [ 51 ].

Traditionally, biomarkers are developed per the principle of Occam’s razor, which posits that natural phenomena should be explained in the simplest form possible, with minimal assumptions [ 52 ]. This i s done to ensure test robustness, reduce intra- and inter-observer variations, and facilitate external validation in diverse patient populations [ 53 ]. The same principle is also used in the development of biomarkers for HCC. Currently the only predictive biomarker with level 1 evidence (proven by randomized trial (s) designed to test biomarker performance and clinical impact, according to the International Liver Cancer Association (ILCA) white paper [ 54 ] is alpha-fetoprotein (AFP) in selecting HCC patients for ramucirumab therapy (an anti-VEGFR antibody) in the second-line setting [ 55 ], although its usefulness is limited given the relatively low absolute survival gain by ramucirumab treatment.

In ICI therapy, tumor PD-L1 expression and tumor mutation burden (TMB) are the most validated predictive biomarker for advanced cancers. More recently, multi-omics approaches are increasingly use to explore the mechanistic interaction among hosts, immune cells, and tumors for biomarker development (Fig.  1 and Table  1 ) [ 56 ]. Expression patterns or ‘signature’ of immune related genes in tumor tissue, particularly those related to inflammation and T cell function, may serve both for prediction of treatment efficacy and for mechanistic exploration [ 57 , 58 ]. Biomarker studies using archival tumor tissues from HCC patients who received anti-PD1/ anti-PDL1 based therapy identified genes associated with inflammation, antigen presentation, interferon responses and cytokine signaling (ILCA level 2–3 evidence) [ 59 , 60 , 61 , 62 , 63 ]. However, findings from these translational studies cannot be easily validated externally because of difficulties in ensuring methodological standardization.

figure 1

Approaches of biomarker development for immunotherapy in HCC. Summary of multi-omics profiling approaches of biomarker development. The biomarkers of DNA, RNA, and proteins are intergraded from different modalities. Each modality exhibits advantages and disadvantages for constructing the entire picture of tumors and microenvironments. WES, whole-exome sequencing, WGS, whole-genome sequencing

The role of epigenetic aberrations, including non‐coding RNA expression, DNA promoter hypo‐ or hyper‐methylation, and histone modifications (e.g., acetylation), in hepatocarcinogenesis and their potential as prognostic or predictive biomarkers have been extensively studied [ 64 ]. Epigenetic aberrations not only contribute to carcinogenesis but also are involved in TME remodeling, immune evasion, and effector T cell exhaustion [ 65 , 66 , 67 ]. Reversing epigenetic aberrations using de-methylating agents, histone deacetylase (HDAC) inhibitors, or enhancer of zeste homologue 2 (EZH2) inhibitors, may increase the efficacy of ICI therapy [ 68 , 69 , 70 ]. Therefore, developing epigenetic biomarkers and targets for immune modulation is another promising approach for enhancing ICI-based combination therapy.

Tissue-based biomarker exploration

Tumor PD-L1 expression is associated with a favorable objective response to anti-PD1/ anti-PD-L1 therapy in both the preclinical models of liver cancer [ 71 ] and in clinical trials on patients with HCC [ 12 , 59 , 63 ]. As shown in Table  1 , higher density of infiltrating T cells, particularly CD8 + T cells, CD3 + T cells, GZMB + CD3 + T cells, as well as MHC class I protein expression were observed in patients responding to combination immunotherapy with atezolizumab and bevacizumab [ 63 ]. Because HCC is associated with a lower TMB compared with other types of cancer, TMB is not useful for predicting immunotherapeutic response in HCC [ 60 , 72 ]. Another likely explanation for this phenomenon is the high intra-tumoral heterogeneity of HCC, which makes obtaining an accurate measurement of the TMB from a single biopsy sample difficult [ 73 , 74 ]. These findings clearly underscore the limitations of the minimalist approach for accurately predicting the therapeutic response in highly heterogeneous types of cancer such as HCC. Activation of the WNT/ β-catenin pathway was associated with inferior treatment efficacy in some [ 75 , 76 ] but not all [ 63 ] studies of patients who received anti-PD1 therapy.

Overall, the composition of genes used to represent specific immune related pathways have varied from one study to another, rendering cross comparisons difficult. For instance, in the CheckMate-040 study of nivolumab, 4 genes, namely CD274 (PD-L1), CD8A, LAG3, and STAT1 , were selected to constitute an inflammation-related gene signature [ 59 ]. By contrast, in the CheckMate459 trial of nivolumab versus sorafenib, the Gajewski inflammation signature [ 77 ] was used to identify patients with better objective response and survival after nivolumab therapy [ 60 ].

The biomarker study for the atezolizumab plus bevacizumab combination therapy integrated data from the IMbrave150 randomized trial (atezolizumab plus bevacizumab versus sorafenib) and an earlier phase I trial to explore predictors of efficacy of the combination treatment and the synergistic immune modulatory mechanisms of anti-VEGF agent [ 63 ]. The team found that a higher objective response rate and longer survival were associated with higher PD-L1 expression, stronger effector T cell signatures ( CXCL9 , PRF1 , and GZMB ), and lower expression of certain metabolism-related pathways (e.g., bile acid, fatty acid). The additional therapeutic benefit of bevacizumab was associated with increased expression of genes related to regulatory T (Treg) cells ( CCR8 , BATF , CTSC , TNFRSF4 , FOXP3 , TNFRSF18 , IKZF2 , and IL2RA) and myeloid inflammation (CXCL1 , CXCL2 , CXCL3 , CXCL8 , IL6 , PTGS1 ). Consistently, elevated expressions of effector T cells and myeloid inflammation signatures have been correlated with improved efficacy of atezolizumab plus bevacizumab for patients with advanced renal cell carcinoma [ 78 ].

The aforementioned findings support the potential use of transcriptomic markers for investigating the mechanisms of ICI-based combination therapy across different types of cancer. Recent advancements in epigenetic signatures have propelled multi-omics analysis into a new frontier [ 79 , 80 ]. Some studies on HCC have established links between epigenetic-related gene signature (extracted from bulk RNA sequencing data) and immunotherapeutic responses [ 81 , 82 ]. Although these studies have provided insights into the complex interactions between different immune cells in regulating antitumor immunity in the TME, a dauntingly high level of analytic expertise is required. In addition, classifying patients into subgroups of high- versus low-expression of specific signatures, based usually on median expression values of the particular patient cohorts, may hinder external validation in different patient cohorts.

Blood-based biomarker exploration

Blood-based biomarker analysis enables non-invasive, real-time monitoring of treatment effects. In patients who received ICI-based therapy, real-time monitoring may aid in the development of pharmacodynamic markers to characterize immune activation after treatment [ 83 ] and differentiate between true and pseudo-progression after treatment [ 84 ]. Biomarkers detected in patients’ blood may reflect the tumor burden [ 85 , 86 ], status of systemic inflammation (e.g., neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR)), and the genetic features associated with specific biological behaviors [ 59 , 87 , 88 , 89 ]. NLR and AFP levels were reported to predict response to ICI-based therapy [ 59 , 85 ]. The CRAFITY score, consisting of serum C-reactive protein and AFP levels [ 90 ], may serve as both a prognostic factor and a predictor of efficacy for ICI-based systemic therapy for patients with advanced HCC [ 91 , 92 ]. These data offer level 2 evidence, in accordance with ILCA guidelines, regarding the use of blood-based biomarkers in patients with advanced HCC. Circulating immune cells, particularly CD8 effector memory T cells and antigen presenting cells (APCs) are linked to objective immunotherapeutic response [ 93 ].

In addition to circulating immune cells, circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) are regarded as potential peripheral biomarkers for predicting immunotherapeutic response (Table  1 ). In patients with advanced HCC who received ICI-based therapy, high ctDNA levels and TERT mutations detected in ctDNA are associated with poor survival outcome [ 88 , 89 ]. However, these biomarkers exhibit complex interactions with each other, and correlation with the same markers at tissue level needs further clarification. For example, genetic studies of the IMbrave150 trial indicated that patients with TERT promoter mutation in tumors are more likely to benefit from the combination therapy [ 63 ], but in another case series HCC patients with TERT mutation detected in circulatory DNA had inferior survival compared with patients without detectable TERT mutation [ 89 ].

The pharmacodynamic monitoring of ICI-based therapy may include analysis of T-cell activation or exhaustion by flow cytometry and T-cell clonality by T-cell receptor sequencing [ 83 ]. A dose optimization study of durvalumab (anti-PDL1) plus tremelimumab (anti-CTLA4) for patients with non-small-cell lung cancer revealed an increasing trend of T cell proliferation and activation in peripheral blood with increasing tremelimumab dosage. The dosage of 1 mg/kg was finally selected based on safety data [ 94 ]. In another similar study on patients with advanced HCC, tremelimumab (300 mg, single-dose) plus durvalumab induced a significant increase in the number of CD8 + Ki67 + T cells, informing the optimal dosage for the HIMALAYA trial [ 95 ]. These pharmacodynamic markers may oversimplify the immune regulatory effects of anti_CTLA4 agents. Preclinical studies suggest that the antitumor efficacy of anti-CTLA4 ICIs involves the inhibition of Treg cells [ 96 , 97 ]. Therefore, more sophisticated technology are required to capture the complex interaction among immune cells in the TME. High dimensional immune-monitoring technologies such as mass cytometry by time-of-flight (CyTOF) combined with single-cell RNA sequencing (scRNA seq) can be used to identify specific immune subsets related to response and immune-related adverse events (irAEs), indicating the possibility of targeting novel immune regulatory pathways to uncouple treatment efficacy and irAEs [ 93 ].

Confounders in the interpretation of biomarker studies

The etiologies of the underlying liver diseases have been extensively studied as confounding factors for the interpretation of clinical trial results. Meta-analyses of clinical trials on sorafenib indicated that patients with HCC and hepatitis C infection may benefit more from sorafenib treatment [ 98 , 99 ]. Although molecular pathogenesis studies have suggested that HCC with different etiologies is associated with different patterns of molecular aberrations, these aberrations are not directly related to the antitumor mechanisms of sorafenib and may not explain the difference in survival benefit among different sub-groups [ 100 ]. For HCC patients with different etiologies, no evident difference in survival benefit was noted for other targeted therapeutic regimens, including lenvatinib, regorafenib, cabozantinib, and ramucirumab [ 55 , 101 , 102 , 103 ].

In ICI therapy, etiology-related debates have focused on non-viral etiologies, particularly non-alcoholic steatohepatitis (NASH) [ 104 ]. Pre-clinical models indicated that diet-induced NASH may compromise T cell function in the liver microenvironment and confer resistance to anti-PD1 therapy [ 104 , 105 , 106 ]. In response to metabolic stimuli, a subgroup of CXCR6 + CD8 T cells was identified to induce liver damage (‘auto-aggressive’) and may induce resistance to antiPD1/ antiPD-L1 therapy [ 104 , 106 ]. A meta-analysis of ICI-based systemic therapy for advanced HCC suggested that patients with hepatitis B (HBV)-related HCC demonstrated more prominent survival benefit, whereas patients with non-viral HCC appeared to benefit the least (Table  2 ) [ 104 ].

However, the difference in survival benefit among HCC patients with viral versus non-viral etiologies was not consistently seen [ 9 , 14 , 107 , 108 ]. The non-viral subgroups included in HCC clinical trials encompass a heterogeneous population of patients with different etiologies or underlying liver diseases which are usually less stringently diagnosed on the basis of current clinical practice guidelines [ 109 ]. In addition, the co-existence of metabolic dysfunction-associated fatty/steatotic liver disease (MAFLD or MASLD) is often overlooked in these trials [ 110 , 111 , 112 ]. MAFLD may coexist in about 10–20% patients with chronic viral hepatitis. It may also exacerbate liver inflammation and fibrosis, leading to poorer clinical outcomes than those of patients without MAFLD [ 111 , 112 , 113 , 114 ]. Therefore, it is reasonable to hypothesize that the presence of MAFLD with chronic viral hepatitis may modulate the immune microenvironment of HCC and complicate the interpretation of biomarkers for immunotherapy.

In addition to the underlying liver diseases, tumor-related features such as hypoxia and epithelial-mesenchymal transitions (EMT) also play important role in determining treatment responses. In a previous study we described the effect of hypoxia on the enrichment of and interaction between immunosuppressive dendritic cells (DCs) and Treg [ 39 ]. Hypoxia may serve as a confounding factor that further attenuates immunotherapeutic responses because of its immunosuppressive effect. Consistent with our findings, those of Kopecka et al. [ 115 ] suggested hypoxia is a potential driver of resistance to immunotherapy. EMT is associated with tumor immune escape [ 116 ], which may regulate the expression of immune checkpoint molecules [ 117 ]. Further research is required to determine the impact of this phenomenon on HCC immunotherapy.

In summary, development of an improved technology or system is required to address the limitations of current biomarkers and the potential confounding effects from underlying etiologies and tumor characteristics.

Creators: advancement in multi-omics approach for translational research in HCC

In published clinical trials of anti-PD1/ anti-PD-L1-based combination therapy for unresectable HCC, efficacy appears to a plateau, with an overall survival of 20 months, a progression-free survival of 7–8 months, and an objective tumor response approximately 25% based on RECIST 1.1 (response evaluation criteria in solid tumors, Table  3 ) [ 48 ]. Several approaches can be considered to enhance the efficacy of systemic therapy. The first approach is combination with agents targeting other immune checkpoints, such as TIGIT (T Cell Immunoreceptor with Ig and ITIM Domains), to enhance T-cell function [ 118 ]. The second approach is targeting mechanisms of resistance to anti-PD1/ anti-PD-L1 therapy identified in pre-clinical research, such as tumor-infiltrating Treg cells [ 39 , 119 ], epigenetic control of immune function [ 120 , 121 ], and other immune-related signaling pathways [ 122 ]. The third approach is exploring novel targets for immune modulation. Further research is required to comprehensively understand the phenotypes and functions of various immune cell subsets within the TME. In recent years, various multi-omics approaches, particularly the single-cell omics (SC-omics) technologies, have been developed, providing a more in-depth understanding of the heterogenous and complex dynamics between different sub-populations within the TME.

SC-omics technologies enable high-throughput profiling of individual cells and play a key role in elucidating the complex interplay between different immune subsets within the TME. These technologies, which encompass proteomics transcriptomics, genomics and even epigenomics, offer valuable insights into the immune evasion mechanisms used by cancer cells and potential targets for immunotherapy by identifying distinct immune cell populations and their associated functional states. Recent developments in single-cell epigenomics analysis, such as in single-cell transposase-accessible chromatin with sequencing [ 123 ] and spatial transcriptomics [ 124 ], have revolutionized our understanding of the TME and its response to immunotherapy. SC-omics approaches are particularly useful in identifying rare cell types, capturing transcriptional heterogeneity within cell populations, and unveiling the dynamic changes in cell states over time. Integrating SC-omics data with other omics approaches can provide a more comprehensive understanding of the molecular mechanisms driving cancer development and progression, thereby guiding the development of personalized cancer therapies.

Multi-omics approaches for understanding the immune mechanisms in HCC

SC-omics analysis has not only facilitated the characterization of the diverse immune cell subsets within the TME but also substantially contributed to the understanding of immune profiles in different disease states and biomarker discovery for immunotherapy in HCC. In an early SC-transcriptomic study, Zheng et al. [ 125 ] analyzed the landscape of T cells in individually sorted CD4 + and CD8 + T cells from TME, non-TME and peripheral blood of patients with HCC. They comprehensively examined various T-cell populations and identified LAYN as the key gene associated with the suppressive function of Treg cells and exhausted CD8 T cells within the TME. In addition to Treg and exhausted CD8 + T cells, they discovered a unique TME-specific CD8 + FOXP3 + regulatory-like cell population, confirmed by multi-color immunohistochemistry (Fig.  2 ). They indicated that this Foxp3 + CD8 + Treg cell subset was characterized by the expression of typical Treg genes, including  FOXP3 ,  CTLA4 ,  TNFRSF9 , and TNFRSF18 , and cytolytic-related genes, including  PRF1 ,  GZMA , and  NKG7 [ 125 ]. Earlier and subsequent studies on Foxp3 + CD8 + Treg cells have suggested an immunosuppressive phenotype [ 126 , 127 ]. Zhang et al. [ 128 ] used a combination of two single-cell RNA sequencing technologies (10 × Genomics and SMART-seq2) to comprehensively analyze the CD45 + immune landscapes of five compartments (tumor, adjacent liver, hepatic lymph node, blood, and ascites) from 16 treatment-naive patients with HCC. Focusing primarily on the role of DCs and TAMs in regulating the functions of lymphocytes in the TME of HCC, the authors examined the key roles of the LAMP3 + DCs and GPNMB- or SLC40A1-expressing TAMs (Fig.  2 ) [ 128 ]. They reported that the LAMP3 + DCs were more likely associated with T-cell dysfunction. In addition, GPNMB + TAMs promoted TNF-α production, whereas SLC40A1 + TAMs promoted pro-inflammatory cytokines such as IL-23 and IL-6 but suppressed IL1b production (Fig.  2 ). The latest addition to this series of single-cell RNA sequencing studies from the same group focused on tumor-infiltrating neutrophils (TANs). They found that the CCL4 + and PD-L1 + TANs were both immunosuppressive and associated with poor prognosis in patients with HCC (Fig.  2 ) [ 129 ]. This series of single-cell analyses of the TME of HCC has unveiled the complex composition and dynamic interaction of tumor-infiltrating immune cells, thereby providing a valuable resource for understanding and developing strategies aimed at modifying the TME to enhance antitumor immunity.

figure 2

Multi-omics analyses of complex dynamics within the TME of HCC. Several immune subsets, which are either immunosuppressive, pro-inflammatory, or cytotoxic, as observed in multi-omics analyses of HCC. Non-immune cells such as the endothelial and tumor cells also play an key role in the TME of HCC. Treg, regulatory T cells; DC, dendritic cells; TAN, tumor-associated neutrophils; TAM, tumor-associated macrophages; APC, antigen-presenting cells; T EM , T-effector memory cells

In addition to the immunophenotyping of the TME of HCC, SC-omics analysis has played a key role in elucidating various immune profiles across different disease states. Nguyen et al. [ 158 ] reported distinct immune landscapes with HCC progression, with the peak of immune evasion observed at the intermediate stage, characterized by accumulation of exhausted CD8 + T cells and Treg cells. Sun et al. [ 130 ] reported an increase in DCs with decreasing antigen-presentation capability and reduced Treg cells in early-relapse HCC cases. They also discovered a unique CD8 + T-cell population enriched in early-relapsed HCC, which expressed KLRB1 (CD161) and displayed an innate-like, low cytotoxic and clonal expansion phenotype (Fig.  2 ). These two studies have indicated that immune evasion is a dynamic process that occurs at different time points along tumor progression and relapse, indicating that anti-CD161 may serve as a potential novel checkpoint target, particularly for relapsed HCC [ 131 ].

Multi-omics analysis has achieved great progress in biomarker discovery for therapeutic response [ 132 , 133 , 134 ]. Ma et al. [ 135 , 136 ] examined the clonal evolution of tumor cells and their interaction with immune cells in patients with HCC and cholangiocarcinoma who received immunotherapy (Fig.  2 ). Sharma et al. [ 137 ] reported a similarity between the immune modulation of fetal liver and the TME of HCC and discovered that VEGF and NOTCH signalling play a functional role in maintaining immune-suppressive onco-fetal reprogramming (Fig.  2 ). This study provides valuable insights into the potential mechanisms and targets of anti-VEGF therapy in HCC. Other studies have indicated that the interaction between effector T cells and DCs [ 93 , 138 ], macrophages, and cancer-associated fibroblasts [ 139 ] regulate immunotherapeutic response. In a study based primarily on the peripheral blood SC transcriptomic analysis, CXCR3 + effector memory CD8 + T cells and HLA-DR + APCs were identified as two key potentially interacting immune cells linked to distinct clinical fates of either response or immune-related adverse effects (irAEs) in patients with HCC who underwent anti-PD-1 therapy (Fig.  2 ) [ 64 ]. Subsequently, a therapeutic strategy was designed to uncouple response and irAEs for optimal therapeutic outcome [ 64 ]. In a more recent study, scRNA-seq and spatial transcriptomic analyses were used to identify a triadic interaction among granzyme K + PD-1 + effector-like CD8 + T cells, CXCL13 + CH25H + IL-21 + PD-1 + CD4 + T helper cells, and LAMP3 + mature DCs enriched in immunoregulatory molecules (mregDC), which are linked to therapeutic response in HCC patients treated with neoadjuvant anti-PD-1 ICIs [ 138 ].

In summary, multi-omics studies have offered a comprehensive and multi-dimensional understanding of the TME, thereby laying the foundation for the discovery of novel therapeutic targets for next-generation immunotherapy [ 132 , 140 ].

Development in multi-omics driven therapeutic design for HCC

At present, the most popular approach in clinical trials is to combine anti-PD1/ anti-PDL1 ICIs with another ICI agent, such as anti-TIM3 [ 141 ], anti-LAG3 [ 142 ], or anti-TIGIT [ 143 ], to enhance the re-invigorating effects of antiPD1/ anti-PDL1 ICIs on exhausted CD8 T cells [ 144 ]. Chiu et al. [ 145 ] compared human HCC to adjacent non-tumor liver tissues and observed an increase in PVRL1 , which stabilizes cell surface poliovirus receptor (PVR) that interacts with TIGIT. They reported that TIGIT inhibition or genetic ablation of PVRL1 increased ratio of cytotoxic CD8 + T cells to Treg cells in murine liver cancer models and sensitized the mice to anti-PD1 therapy (Table  4 ). Wei et al. [ 146 ] identified a signaling pathway linking protein kinase C alpha (PKCα), the transcription factor ZPF64, and colony-stimulating factor-1 (CSF-1), which plays a key role in polarization of TAMs towards an immunosuppressive M2 phenotype in the TME of HCC and resistance to anti-PD-1 therapy. They also discovered potent antitumoral activity in preclinical models when inhibitors targeting PKCα (Gö6976) or CSF1 (BLZ945) were combined with anti-PD-1 therapy, suggesting new options for reversing resistance to anti-PD-1 therapy (Table  4 ).

Because the efficacy and adverse events of ICI therapy are both immune-related, uncoupling these events to enhance efficacy without aggravating adverse events will greatly improve the therapeutic index of new combination regimens. Chuah et al. [ 93 ] identified the interaction between CXCR3 + effector memory CD8 + T cells and HLA-DR + APCs as a key mechanism determining response versus irAEs in patients with HCC treated with anti-PD-1 ICI. They identified TNFR2 as a key biomarker specifically linked to clinical response but not irAEs, and demonstrated enhanced therapeutic response without increased irAEs in preclinical models by combination of anti-TNFR2 and anti-PD-1. They also discovered that TNFR2 was specifically enriched in Treg cells within the TME of HCC, indicating a potential tumor Treg-specific target (Fig.  2 ). Overall, these findings may facilitate the development of therapeutic strategies aimed at uncoupling therapeutic response and irAEs to optimize therapeutic outcome (Table  4 ).

Multiple studies have examined the mechanisms underlying the immune-suppressive TME associated with NASH- or MASLD-related HCC [ 147 ]. According to preclinical models, the NASH microenvironment may induce CD8 T-cell subpopulations that caused liver damage [ 106 ] or even promote HCC development [ 104 ]. Wabitsch et al. [ 105 ] reported that the metabolic reprogramming of hepatic CD8 + T cells resulted in impaired motility and resistance to anti-PD-1 therapy in murine NASH-HCC models. They indicated that this dysfunctional CD8 + T-cell phenotype was reversed by metformin treatment (Table  4 ). Many studies have extensively examined the cancer-preventing effects of metformin, and numerous mechanisms have been proposed [ 148 , 149 , 150 , 151 ]. Leslie et al. [ 147 ] identified TANs, which over-expressed the neutrophil receptor CXCR2, as key factors underlying the inferior efficacy of anti-PD-1 therapy in NASH-related HCC. They reported that combining anti-PD-1 with AZD5069, a CXCR2 inhibitor, led to the reprogramming of TANs to a more proliferative and inflammatory phenotype, increased intra-tumoral XCR1 + DCs and CD8 + T-cell infiltration, and enhanced anti-tumor response in NASH-HCC models (Table  4 ). In summary, multi-omics approaches can be used to clarify the immune modulatory mechanisms of the underlying liver diseases and to identify novel therapeutic targets in the TME of HCC.

Research into the immunomodulatory effects of MKIs should not be limited to their anti-angiogenic properties. Lenvatinib may inhibit the PKCα/ZFP64/CSF1 [ 146 ] and transforming growth factor-β signaling pathways in the TME of HCC (Table  4 ) [ 152 ]. Cabozantinib may also increase neutrophil chemotaxis, induce infiltration of TANs [ 153 ] with a more cytotoxic N1 phenotype [ 154 ], and reduce intra-tumoral myeloid-derived suppressor cells (MDSCs) (Table  4 ) [ 155 ]. Although these immunomodulatory mechanisms of MKIs may enhance effector T-cell infiltration and response to anti-PD1 therapy in preclinical HCC models, the lack of additional survival benefits provided by combination therapy in randomized clinical trials indicates that additional comprehensive mechanistic studies are required to determine whether and how these mechanisms enhance antitumor immunity in clinical settings.

Epigenetic regulation plays a key role in modulating antitumor immune response through both innate and adaptive immunity. Epigenetic modifiers such as de-methylating agents, HDAC inhibitors, and EZH2 inhibitors, can activate NK cells and macrophages, reverse CD8 T-cell exhaustion, and suppress Treg-mediated immune suppression [ 67 , 70 ]. Among all types of epigenetic modifiers, HDAC inhibitors are the most widely evaluated in pre-clinical models of HCC [ 120 , 156 , 157 ]. Nevertheless, identifying the most relevant cellular and molecular targets of HDAC inhibitors is a challenging task. Therefore, conducting multi-omics analyses at the single-cell level can aid in elucidating the evolution of immune cells, dissecting the intra-tumor heterogeneity, and identifying rare but functionally essential cell populations [ 21 ].

Future perspectives

In this review, we highlighted the potential of advanced technologies in addressing the limitations in the current process of drug development and biomarkers discovery for HCC. These technologies can provide a more comprehensive understanding of the heterogeneity and complexity of the TME, which can consequently clarify the mechanisms underlying various treatment options for HCC. As creators, translational researchers should be aware of the most recent advance of the novel technologies to rapidly and accurately identify new biomarkers and treatment options.

Integrating advanced multi-omics technologies into clinical trials, from early proof-of-concept trials involving novel combination strategies to pivotal trials versus the current standard of care, requires close collaboration between translational researchers and clinical trial specialists to push the frontiers of HCC treatment toward a definitive cure.

Availability of data and materials

Not applicable.

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The authors would like to thank the Liver Disease Prevention & Treatment Foundation, Taiwan, for logistic support.

This paper was supported by Grants MOHW112-TDU-B-221-124007 (from Ministry of Health and Welfare, Taiwan), 111-2314-B-002 -039 (from National Science & Technology Council, Taiwan), NTUH-112L892101, VN112-12 (from National Taiwan University Hospital) (to Dr. Hsu) and National Medical Research Council (NMRC), Singapore (ref numbers: NMRC/CSA-SI/0013/2017, NMRC/CSA-SI/0018/2017, NMRC/OFLCG/003/2018) as well as Duke-NUS Khoo Bridge Funding Award (Duke-NUS-KBrFA/2022/0058) and International Gilead Sciences Research Scholars Program in Liver Disease—Asia (to Dr. Chew).

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Chien-Huai Chuang & Chiun Hsu

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CH and VC conceptualized the overall scope of this review article. VC, CHC, and CH reviewed and analyzed the data reported in the literature. VC and CH drafted the manuscript. All authors read and approved the final manuscript.

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Dr. Chiun Hsu received research grants from Bristol-Myers Squibb (BMS)/ ONO, Roche, and Ipsen and received honorarium from the following pharmaceutical companies: AstraZeneca, Bayer, BMS/ONO, Eisai, MSD, Novartis, Roche, TTY Biopharm. Dr. Chew and Dr. Chuang declared that they had no competing interests to disclose.

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Chew, V., Chuang, CH. & Hsu, C. Translational research on drug development and biomarker discovery for hepatocellular carcinoma. J Biomed Sci 31 , 22 (2024).

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Received : 03 September 2023

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    research on something related to the course. Even if the instructor has introduced the assignment in class, make sure to read the ... Tips for Organizing Your Essay If you are used to writing essays that are similar to the five-paragraph essay (one claim and then three points that support that claim), it can be daunting to think about how to ...

  24. Key influences on university students' physical activity: a systematic

    Key articles were also selected for citation searching via Scopus. In consultation with a librarian, these databases were selected due to their unique scope, relevance, broad coverage, and utility. This process ensured the identified literature aligned with the aim and research topic of our systematic review.

  25. Translational research on drug development and biomarker discovery for

    Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist in this field because of the limited availability of human tumor samples from surgery, the lack of homogenous oncogenic driver mutations, and the paucity of adequate experimental models. In this review, we provide insights into these ...

  26. The Role of Intersectionality and Context in Measuring Gender-Based

    Research article. First published online February 19, 2024. ... Conclusion. Gender-based violence has consequences at the individual, institutional, and societal levels, though knowledge about the extent of the problem within universities and other research organizations is limited. Eradicating gender-based violence in this context cannot be ...

  27. The associations of "weekend warrior" and regularly active physical

    INTRODUCTION. Obesity is a heterogeneous disorder that affects 650 million adults and causes great health and economic burdens worldwide [(1, 2)].It has been identified as a risk factor for a set of chronic diseases, cancers, and osteoarthritis [(3-5)].Different fat deposition leads to various metabolic profiles and associations of cardiovascular and metabolic risk.

  28. Full article: Laughing the Pain Away: Understanding Sambat Practice

    Conclusion. This article provides an empirical analysis of the relationship of language use and emotional attribution to cultural practice. It provides insight into how a speech genre embedded in a traditional practice shifted the value of language features used within the practice. ... Jurnal Komunitas: Research and Learning in Sociology and ...

  29. Superionic lithium transport via multiple coordination environments

    In most solid electrolytes, the conduction pathways have a single coordination geometry. Han et al. designed electrolytes based on a Li 7 Si 2 S 7 I chemistry with ion arrangements similar to those in intermetallic systems. This leads to anion packing that alternates between hexagonal close packed structures and sheared face-centered cubic-like motifs to accommodate sulfur and iodine complexes ...