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BMC Medicine (2025) 23:477 [https://doi.org/10.1186/s12916-025-04306-5](https://doi.org/10.1186/s12916-025-04306-5)  \nBMC Medicine  \n REVIEW Open Access  \nCircRNAs: functions and emerging roles in cancer and immunotherapy  \nYan Wang1†, Yanru Cui2†, Xin Li1†, Su-Han Jin3, Haitao Wang4, Udo S. Gaipl5,6,7, Hu Ma1*†, Shixiang Wang8*† and Jian-Guo Zhou 1,5*†  \nAbstract  \nBackground Circular RNAs (circRNAs) are emerging as promising tools in cancer and immunotherapy, with unique characteristics that offer potential therapeutic applications.  \nMain body This review outlines the discovery, biogenesis, and mechanisms of circRNAs, emphasizing their roles in cancer and immune regulation. CircRNAs modulate immune responses by acting as miRNA sponges, binding RNA-binding proteins, or serving as translation templates. These interactions influence T cells, NK cells, macrophages, and immune checkpoints. The review also explores circRNAs’ roles in different cancers, focusing on target identification, immune effects, and mechanisms of action. Additionally, it examines circRNA-based therapies, including vaccines, CAR-T cell therapy, and database applications.  \nConclusion Despite their potential, technical hurdles must be overcome to advance circRNAs’ clinical use in cancer immunotherapy. Future research should focus on addressing these challenges to fully realize the therapeutic potential of circRNAs.  \nKeywords CircRNAs, Cancer, Biomarkers, Immunotherapy, Tumor vaccines  \n\n| †Yan Wang, Yanru Cui, and Xin Li contributed equally to this work as first authors. |\n| --- |\n| †Hu Ma, Shixiang Wang, and Jian-Guo Zhou contributed equally to this work as last authors. |\n\n*Correspondence: Hu Ma[mahuab@163.com](mahuab@163.com)[ ](mahuab@163.com)Shixiang Wang [wangshx@csu.edu.cn](wangshx@csu.edu.cn)[ ](wangshx@csu.edu.cn)Jian-Guo Zhou  \n[jianguo.zhou@zmu.edu.cn](jianguo.zhou@zmu.edu.cn)  \n1 Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China  \n2 Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA  \n3 Department of Orthodontics, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, China  \n4 Center for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China  \n5 Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität ErlangenNürnberg, Erlangen, Germany  \n6 Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany  \n7 FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-AlexanderUniversität Erlangen-Nürnberg, Erlangen, Germany  \n8 Department of Biomedical Informatics, School of Life Sciences, Central South University, Changsha, China  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/.)[.](http://creativecommons.org/licenses/by-nc-nd/4.0/.)  \nWang et al. BMC Medicine (2025) 23:477  \nBackground  \nCircular ","cbCaiePHLriPoaVA","https://ap.wps.com/l/cbCaiePHLriPoaVA","pdf",1727614,18,"English","# Abstract\n# Background\n# Main body\n## Mechanisms of circRNAs in cancer and immunity\n## Roles in immune cells and immune checkpoints\n## CircRNAs-based therapies and applications\n# Conclusion","[{\"question\":\"What are circRNAs and why are they considered promising for immunotherapy?\",\"answer\":\"CircRNAs are non-coding RNAs with a covalently closed-loop structure. Their distinctive properties make them promising tools for cancer immunotherapy because they can regulate immune-related processes and support therapeutic applications.\"},{\"question\":\"How do circRNAs modulate immune responses?\",\"answer\":\"CircRNAs modulate immunity by functioning as miRNA sponges, binding RNA-binding proteins, and acting as translation templates. These interactions influence immune cell behavior and immune checkpoint regulation.\"},{\"question\":\"What directions does the review identify for future circRNA research in cancer immunotherapy?\",\"answer\":\"The review stresses that technical hurdles need to be overcome to advance circRNAs toward clinical use. Future work should address these challenges to realize their therapeutic potential.\"}]","CircRNAs: functions and emerging roles in cancer and immunotherapy | PDF",1790190649,45]