Research progress on tumor microenvironment of gastrointestinal stromal tumor

Chen Guanyu; Qin Geng; Du Shiyu

doi:10.3760/j.issn.1673-4777.2026.05.030

Abstract：Gastrointestinal stromal tumor(GIST)is the most common soft tissue sarcoma,and its initia-tion and progression are mainly driven by activating mutations in KIT or platelet-derived growth factor receptor a 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 extracel-lular 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.