免疫治疗在胃肠间质瘤中的研究现状和展望

Research status and prospect of immunotherapy in gastrointestinal stromal tumors

酪氨酸激酶抑制剂(TKI)的出现显著降低了胃肠间质瘤(GIST)患者的复发转移风险并延长了生存期,但耐药的发生常常不可避免。免疫治疗已经在多种实体肿瘤中被证明有效,但在GIST中的疗效尚不明确。免疫治疗的疗效取决于肿瘤微环境,肿瘤浸润免疫细胞和免疫检查点是肿瘤微环境的重要组成部分,它不仅参与调控局部肿瘤的免疫应答,还是免疫治疗的靶点,对其进行全面的分析可以了解肿瘤免疫逃逸的机制。本综述回顾相关文献,发现GIST患者有着丰富的肿瘤浸润免疫细胞,其在肿瘤的免疫监视和逃逸过程中发挥重要作用。虽然早期临床研究显示,患者对于免疫治疗具有良好的耐受性,但疗效却不如人愿。因此,如何筛选出GIST免疫治疗的获益人群、协调免疫治疗和TKI治疗的关系是下一步需要探索的关键问题。同时,基础研究和大样本前瞻性临床试验的逐渐深入,将会为GIST中免疫治疗的应用提供更多的策略。

Tyrosine kinase inhibitors(TKI)significantly reduce the risk of recurrence and metastasis and prolong survival in patients with gastrointestinal stromal tumors(GIST),but drug resistance is often inevitable.Immunotherapy has been proven effective in multiple solid tumors,but the efficacy in GIST is unclear.The efficacy of immunotherapy depends on the tumor microenvironment(TME).Tumor-infiltrating immune cells and immune checkpoints are important components of TME,which not only participate in the regulation of tumor immune response but are also the key target of immunotherapy.A comprehensive analysis of them can clarify the mechanism of tumor immune escape.This review found that there are abundant tumor-infiltrating immune cells in GIST,which play an important role in tumor immune surveillance and escape.Although early clinical studies have shown that patients with GIST have a good tolerance to immunotherapy,the curative effect is not satisfactory.Therefore,how to select the responders of immunotherapy and coordinate the relationship between immunotherapy and TKIs is the key issue to be explored.At the same time,the gradual deepening of basic research and large sample prospective clinical trials will certainly provide more strategies for the application of immunotherapy in GIST.