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Chinese Archives of General Surgery(Electronic Edition) ›› 2026, Vol. 20 ›› Issue (05): 340-345. doi: 10.3877/cma.j.issn.1674-0793.2026.05.009

• Review • Previous Articles    

Mechanisms of resistance and strategies for chimeric antigen receptor T cell therapy in gastrointestinal cancers

Biao Liu, Cheng Yang, Zhonghua Shang†()   

  1. Department of General Surgery, the Second Clinical Medical College of Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2025-10-29 Online:2026-10-01 Published:2026-10-13
  • Contact: Zhonghua Shang

Abstract:

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment paradigm for hematologic malignancies, but its success in solid tumors, especially gastrointestinal (GI) cancers including gastric, colorectal, and pancreatic cancers, remains limited. Multiple complex resistance mechanisms constitute major obstacles to its advancement. We classify resistance mechanisms into three categories: tumor-intrinsic factors, immunosuppressive tumor microenvironment, and intrinsic limitations of CAR-T cells themselves. For each resistance mechanism, we discuss corresponding cutting-edge strategies, including next-generation armored CAR-T designs, rational combination therapies with immunomodulators, and novel approaches targeting epigenetic regulation and cellular metabolism.

Key words: Receptors, chimeric antigen, T-lymphocytes, Immunotherapy, Solid tumors, Gastrointestinal cancers

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