| Category |
Immunology |
| Manuscript Type |
Review |
| Article Title |
Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions
|
| Manuscript Source |
Invited Manuscript |
| All Author List |
Dian-Bao Zuo, Zi-Hao Chen, Yu-Meng Jin, Ming Sang, Xiao-Dong Sun, Ai Guo, Xiao-Yang Li, Jin-Xiang Wu, Kang-Kang Ji and Hai Zhou |
| 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 |
| Natural Science Foundation of Hubei Provincial Department of Education |
B2024107 |
| Innovative Research Programme for Graduates of Hubei University of Medicine |
S202513249008 |
| Faculty Development Grants of Hubei University of Medicine |
2024QDJZR037 |
|
| Corresponding Author |
Hai Zhou, Associate Professor, Chief Physician, MD, PhD, Department of Neurosurgery, Binhai County People’s Hospital, No. 299 Coastal Avenue, Yancheng 224500, Jiangsu Province, China. zhouhai3212@163.com |
| Key Words |
Chimeric antigen receptor T therapy; Gamma chain cytokines; Solid tumors; Tumor microenvironment; Clinical translation |
| Core Tip |
Gamma chain (γc) cytokines [interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, IL-21], signaling through the shared γc-Janus kinase 1/3-signal transducer and activator of transcription pathway, critically enhance chimeric antigen receptor T (CAR-T) cell efficacy by modulating proliferation, stemness maintenance, metabolic fitness, and resilience to the immunosuppressive tumor microenvironment. Strategic application, via cytokine selection, spatiotemporal delivery, multi-factor synergy, or genetic engineering (e.g., cytokine-secreting/γc receptor-chimeric CAR-Ts), overcomes key bottlenecks in solid tumor treatment. Clinical breakthroughs, such as IL-15-armored glypican-3 CAR-T and IL-7/C-C motif chemokine ligand 19-co-expressing 7 × 19 CAR-T, demonstrate improved persistence and objective responses, advancing CAR-T therapy from hematologic malignancies toward controllable solid tumor interventions. |
| Citation |
Zuo DB, Chen ZH, Jin YM, Sang M, Sun XD, Guo A, Li XY, Wu JX, Ji KK, Zhou H. Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions. World J Clin Oncol 2026; In press |
| ISSN |
2218-4333 (online) |
| Open Access |
This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/ |
| Copyright |
© The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved. |
| Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
|
| Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
| Website |
http://www.wjgnet.com |
