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中华普通外科学文献(电子版) ›› 2026, Vol. 20 ›› Issue (05) : 340 -345. doi: 10.3877/cma.j.issn.1674-0793.2026.05.009

综述

嵌合抗原受体T细胞治疗胃肠道癌症的耐药机制与对策
刘彪, 杨成, 商中华†()   
  1. 030001 太原,山西医科大学第二临床医学院 山西医科大学第二医院普通外科
  • 收稿日期:2025-10-29 出版日期:2026-10-01
  • 通信作者: 商中华

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 Published:2026-10-01
  • Corresponding author: Zhonghua Shang
引用本文:

刘彪, 杨成, 商中华. 嵌合抗原受体T细胞治疗胃肠道癌症的耐药机制与对策[J/OL]. 中华普通外科学文献(电子版), 2026, 20(05): 340-345.

Biao Liu, Cheng Yang, Zhonghua Shang. Mechanisms of resistance and strategies for chimeric antigen receptor T cell therapy in gastrointestinal cancers[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2026, 20(05): 340-345.

嵌合抗原受体(CAR)T细胞疗法革命性地改变了血液系统恶性肿瘤的治疗格局,但在实体瘤,尤其是胃肠道癌症(胃癌、结直肠癌、胰腺癌等)中取得的成就有限。多重复杂耐药机制是其发展的主要障碍。本综述将耐药机制分为肿瘤固有因素、免疫抑制性肿瘤微环境、CAR-T细胞自身局限性3个方面,针对每种耐药机制讨论相应的尖端策略,包括下一代装甲型CAR-T设计、与免疫调节剂的合理联合治疗,以及针对表观遗传调控和细胞代谢的新方法。

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.

图1 嵌合抗原受体T细胞治疗(CAR-T)细胞疗法的核心流程示意图
图2 胃肠道癌症耐药机制分层图 转化生长因子β(TGF-β);白细胞介素-10(IL-10);嵌合抗原受体(CAR)
表1 CAR-T细胞治疗的靶点及其相关临床试验
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