Wu JX, Jin YM, Shen WJ, Chen ZH, Zuo DB, Chen GP, Ji KK. Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation. World J Clin Oncol 2026; 17(8): 121101 [DOI: 10.5306/wjco.121101]
Corresponding Author of This Article
Kang-Kang Ji, PhD, Associate Research Scientist, Department of Respiratory and Critical Care Medicine, Binhai County People’s Hospital, Binhai Clinical College, Yangzhou University Medical College, No. 299 Haibin Road, Yancheng 224500, Jiangsu Province, China. kyrie@mail.ustc.edu.cn
Research Domain of This Article
Immunology
Article-Type of This Article
review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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Wu JX, Jin YM, Shen WJ, Chen ZH, Zuo DB, Chen GP, Ji KK. Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation. World J Clin Oncol 2026; 17(8): 121101 [DOI: 10.5306/wjco.121101]
Jin-Xiang Wu, Yu-Meng Jin, Wen-Jie Shen, Institute of Medicine Nursing, Hubei University of Medicine, Shiyan 448000, Hubei Province, China
Zi-Hao Chen, Commercialization Center of Scientific and Technical Achievement, Postgraduate Union Training Base of Xiangyang No. 1 People’s Hospital, Huazhong Agricultural University, Xiangyang 441000, Hubei Province, China
Dian-Bao Zuo, Commercialization Center of Scientific and Technical Achievement, Xiangyang No. 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang 441000, Hubei Province, China
Guo-Ping Chen, Kang-Kang Ji, Department of Respiratory and Critical Care Medicine, Binhai County People’s Hospital, Binhai Clinical College, Yangzhou University Medical College, Yancheng 224500, Jiangsu Province, China
Co-first authors: Jin-Xiang Wu and Yu-Meng Jin.
Author contributions: Wu JX and Jin YM contributed equally to this manuscript and are co-first authors. Wu JX, Zuo DB, and Ji KK advanced the primary argument of this review; Wu JX, Jin YM, Shen WJ, Chen ZH, and Chen GP wrote the manuscript; Zuo DB and Ji KK provided important insights. All authors have read and approved the final manuscript.
AI contribution statement: No AI tool was used.
Supported by the Faculty Development Grants of Xiangyang No. 1 People’s Hospital Affiliated to Hubei University of Medicine, No. XYY2025D05; Faculty Development Grants of Hubei University of Medicine, No. 2024QDJZR037; the Natural Science Foundation of Hubei Provincial Department of Education, No. B2024107; Innovative Research Program for Graduates of Hubei University of Medicine, No. S202513249008; Yancheng Applied Basic Research Program, No. YCBK2025128; Jiangsu Youth Science and Technology Talent Support Program, No. JSTJ-2025-934; and Hubei Provincial Natural Science Foundation, No. 2026AFB022.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Kang-Kang Ji, PhD, Associate Research Scientist, Department of Respiratory and Critical Care Medicine, Binhai County People’s Hospital, Binhai Clinical College, Yangzhou University Medical College, No. 299 Haibin Road, Yancheng 224500, Jiangsu Province, China. kyrie@mail.ustc.edu.cn
Received: March 17, 2026 Revised: July 6, 2026 Accepted: August 10, 2026 Published online: August 24, 2026 Processing time: 161 Days and 19.7 Hours
Core Tip
Core Tip: Interleukin-21 (IL-21) mediates dual antitumor effects by enhancing effector immunity and reducing immunosuppression, primarily through the Janus kinase-signal transducer and activator of transcription 3 pathway, which regulates multiple immune cell types. It has also shown synergistic effects in combination with various cancer therapies, including immune checkpoint inhibitors and adoptive cell therapy. However, clinical translation has been hindered by its short half-life and dose-limiting systemic toxicity. This review summarizes the regulatory mechanisms of IL-21, progress in combination regimens, challenges in clinical development, and recent strategies to optimize its therapeutic use. Our goal is to provide a theoretical basis for developing safer and more effective IL-21-based combination immunotherapies for cancer.
