Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, CA, USA.
Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Curr Treat Options Oncol. 2021 Jan 5;22(1):9. doi: 10.1007/s11864-020-00806-z.
The role of targeted therapy is firmly established for gastrointestinal stromal tumors (GISTs); other modalities for targeting this disease are necessary for recurrent and refractory disease. There are several lines of evidence pointing to an active role of the immune system in GIST. Preclinical and clinical studies revealed that the most common type of immune cell infiltration in GISTs is tumor-associated macrophages (TAMs). The mechanism of how TAMs sculpt the tumor microenvironment in GIST is not clear, but it seems that the presence of immunosuppressive regulatory T cells (Tregs) is correlated with the number of TAMs, thus linking macrophages to immunosuppression. CD3+ T cells and NK infiltrates are found in the GIST microenvironment and carry some prognostic value. In early clinical trials, there is evidence for an active role for immunotherapy in treating GIST patients. Moreover, preclinical evidence has indicated that combining TKIs with checkpoint blockers may be synergistic in murine GIST models. Overall, there is substantial preclinical and clinical evidence to support a role for immunoregulation in GIST and further studies will be important for the development of immunotherapies for GIST.
靶向治疗在胃肠道间质瘤（GIST）中的作用已得到充分确立；对于复发性和难治性疾病，需要其他靶向治疗方法。有几项证据表明免疫系统在 GIST 中发挥积极作用。临床前和临床研究表明，GIST 中最常见的免疫细胞浸润类型是肿瘤相关巨噬细胞（TAMs）。TAMs 如何塑造 GIST 肿瘤微环境的机制尚不清楚，但似乎存在免疫抑制调节性 T 细胞（Tregs）与 TAMs 的数量相关，从而将巨噬细胞与免疫抑制联系起来。CD3+T 细胞和 NK 浸润存在于 GIST 微环境中，并具有一定的预后价值。在早期临床试验中，免疫疗法在治疗 GIST 患者中的积极作用有证据支持。此外，临床前证据表明，在小鼠 GIST 模型中，TKI 与检查点抑制剂联合使用可能具有协同作用。总的来说，有大量的临床前和临床证据支持免疫调节在 GIST 中的作用，进一步的研究对于开发 GIST 的免疫疗法将是重要的。
