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World J Gastroenterol. May 28, 2026; 32(20): 115336
Published online May 28, 2026. doi: 10.3748/wjg.v32.i20.115336
Published online May 28, 2026. doi: 10.3748/wjg.v32.i20.115336
MFSD2A suppresses CD8+ T cell exhaustion in colorectal cancer by inhibiting ERK/p38 MAPK-PD-L1 signaling
Shu-Jiong Feng, Yi-Feng Zhou, Jian-Feng Yang, Yi-Shen Mao, Wen-Li Ruan, Xiao-Feng Zhang, Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310000, Zhejiang Province, China
Shu-Jiong Feng, Yi-Feng Zhou, Jian-Feng Yang, Yi-Shen Mao, Wen-Li Ruan, Xiao-Feng Zhang, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
Shu-Jiong Feng, Yi-Feng Zhou, Jian-Feng Yang, Yi-Shen Mao, Wen-Li Ruan, Xiao-Feng Zhang, Hangzhou Institute of Digestive Diseases, Hangzhou 310000, Zhejiang Province, China
Shu-Jiong Feng, Yi-Feng Zhou, Jian-Feng Yang, Yi-Shen Mao, Wen-Li Ruan, Xiao-Feng Zhang, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou 310000, Zhejiang Province, China
Co-corresponding authors: Yi-Feng Zhou and Xiao-Feng Zhang.
Author contributions: Feng SJ contributed to conceptualization and designed the study; Zhou YF conducted the experiments and provided software support; Yang JF and Mao YS performed data analysis; Ruan WL conducted investigations; Zhang XF provided methodological support and conducted data organization; Zhou YF and Zhang XF contributed equally as co-corresponding authors. All authors contributed to the writing-draft, writing-revision, and approved to submit the final version.
Supported by Medical and Health Science and Technology Planning Project of Zhejiang Province, No. 2025KY1188; and The Key Research and Development Program of Zhejiang Province, No. 2023C03054.
Institutional animal care and use committee statement: All animal experiments were conducted according to a protocol approved by the Institutional Animal Care and Use Committee of the Zhejiang Center of Laboratory Animals, No. ZJCLA-IACUC-20020244.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Data are available upon reasonable requests from the corresponding author.
Corresponding author: Xiao-Feng Zhang, Department of Gastroenterology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, No. 261 Huansha Road, Hangzhou 310000, Zhejiang Province, China. zhangxiaofengsy@sina.com
Received: October 17, 2025
Revised: January 10, 2026
Accepted: March 12, 2026
Published online: May 28, 2026
Processing time: 218 Days and 5.1 Hours
Revised: January 10, 2026
Accepted: March 12, 2026
Published online: May 28, 2026
Processing time: 218 Days and 5.1 Hours
Core Tip
Core Tip: Major facilitator superfamily domain containing 2A, a known tumor suppressor and lipid transporter, is identified as a novel immune regulator in colorectal cancer. Major facilitator superfamily domain containing 2A exerts dual antitumor effects by suppressing the extracellular signal-regulated kinase/p38 mitogen-activated protein kinase-programmed death-ligand 1 signaling axis, thereby alleviating CD8+ T cell exhaustion and providing a potential strategy to overcome immunotherapy resistance in colorectal cancer.