2026 年第 5 期 第 21 卷

胃肠道间质瘤肿瘤微环境研究进展

Research progress on tumor microenvironment of gastrointestinal stromal tumor

作者：陈冠妤1秦耿2杜时雨2

英文作者：Chen Guanyu1 Qin Geng2 Du Shiyu2

单位：1中日友好医院（中日友好临床医学研究所）北京协和医学院中国医学科学院，北京100029；2中日友好医院（中日友好临床医学研究所）消化科，北京100029

英文单位：1China-Japan Friendship Hospital(China-Japan Friendship Institute of Clinical Medical Science) Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100029 China; 2Department of Gastroenterology China-Japan Friendship Hospital(China-Japan Friendship Institute of Clinical Medical Science) Beijing 100029 China

关键词：胃肠道间质瘤；肿瘤微环境；靶向治疗；免疫细胞

英文关键词：Gastrointestinalstromaltumors;Tumormicroenvironment;Targetedtherapy;Immunecells

• 摘要：

• 胃肠道间质瘤（GIST）是最常见的软组织肉瘤，其发生发展主要依赖KIT或血小板源性生长因子受体α基因的激活突变驱动。尽管以伊马替尼为代表的酪氨酸激酶抑制剂显著改善了患者预后，但耐药的出现提示仅从肿瘤细胞内在突变难以全面解释GIST的生物学异质性及治疗结局差异。近年来的研究表明，肿瘤微环境（TME）在GIST的进展、免疫逃逸及靶向治疗耐药中发挥关键调控作用。本文系统综述了GIST TME的组成与功能特征，重点整合固有免疫细胞、适应性免疫细胞及间质细胞在肿瘤演化和治疗反应中的作用机制。现有证据显示，免疫细胞与间质内细胞通过免疫抑制、代谢重编程及细胞外基质重塑，与肿瘤细胞形成高度动态的相互作用网络。这一网络共同塑造GIST的免疫生态并影响伊马替尼疗效。值得注意的是，靶向治疗可双向重塑微环境，在激活抗肿瘤免疫的同时诱导免疫抑制性重构。总体而言，GIST的生物学行为和耐药形成是肿瘤内在信号与TME协同作用的结果。深入解析GIST TME的动态特征，有助于发现新的生物标志物，并为靶向治疗与免疫及微环境干预相结合的联合治疗策略提供理论依据。

• Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma, and its initiation and progression are mainly driven by activating mutations in KIT or platelet-derived growth factor receptor α gene. Although tyrosine kinase inhibitors represented by imatinib have significantly improved patient prognosis, the emergence of drug resistance suggests that intrinsic mutations in tumor cells alone cannot fully explain the biological heterogeneity and differential therapeutic outcomes of GIST. Recent studies have demonstrated that the tumor microenvironment (TME) plays a critical regulatory role in GIST progression, immune escape, and resistance to targeted therapy. This article systematically reviews the composition and functional characteristics of the GIST TME, focusing on the mechanisms of innate immune cells, adaptive immune cells, and stromal cells in tumor evolution and therapeutic response. Available evidence indicates that immune cells and stromal cells form a highly dynamic interaction network with tumor cells through immunosuppression, metabolic reprogramming, and extracellular matrix remodeling. This network collectively shapes the immune ecosystem of GIST and affects the efficacy of imatinib. Notably, targeted therapy can bidirectionally remodel the microenvironment, activating anti-tumor immunity while inducing immunosuppressive remodeling. Overall, the biological behavior and drug resistance of GIST result from the synergistic effects of intrinsic tumor signaling and the TME. An in-depth understanding of the dynamic characteristics of the GIST TME will facilitate the discovery of novel biomarkers and provide a theoretical basis for combination therapeutic strategies integrating targeted therapy with immunological and microenvironmental interventions.