Publication Name	World Journal of Clinical Oncology
Manuscript ID	121101
DOI	10.5306/wjco.121101
Country	China

Category	Immunology
Manuscript Type	Minireviews
Article Title	Advancing interleukin-21 in cancer immunotherapy: Mechanisms of action and clinical translation
Manuscript Source	Invited Manuscript
All Author List	Jin-Xiang Wu, Yu-Meng Jin, Wen-Jie Shen, Zi-Hao Chen, Dian-Bao Zuo, Guo-Ping Chen and Kang-Kang Ji
Funding Agency and Grant Number	Funding Agency Grant Number Faculty Development Grants of Xiangyang No. 1 People’s Hospital Affiliated to Hubei University of Medicine XYY2025D05 Faculty Development Grants of Hubei University of Medicine 2024QDJZR037 Natural Science Foundation of Hubei Provincial Department of Education B2024107 Innovative Research Program for Graduates of Hubei University of Medicine S202513249008 Yancheng Applied Basic Research Program YCBK2025128 Jiangsu Youth Science and Technology Talent Support Program JSTJ-2025-934 Hubei Provincial Natural Science Foundation 2026AFB022
Corresponding Author	Kang-Kang Ji, Associate Research Scientist, PhD, 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
Key Words	Interleukin-21; Anti-tumor immunity; Combination therapy; Oncology; Cancer immunotherapy; Clinical translation
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.
Citation	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; In press DOI: https://doi.org/10.5306/wjco.121101
PDF	121101-in-press.pdf

Received	2026-03-17 03:21
Peer-Review Started	2026-03-17 03:21
First Decision by Editorial Office Director	2026-04-10 09:06
Return for Revision	2026-04-10 09:06
Revised	2026-07-06 09:41
Publication Fee Transferred
Second Decision by Editor	2026-08-06 02:38
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-08-10 10:03
Articles in Press	2026-08-10 10:03
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2218-4333 (online)
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