γδ T 细胞是一种罕见但有效的 T 细胞亚群，具有多效性功能。它们通常存在于肿瘤内，但 γδ T 细胞对酪氨酸激酶抑制的反应尚不清楚。为了解决这个问题，我们研究了一种胃肠道间质瘤 (GIST) 的基因工程小鼠模型，该模型由对 Kit 抑制剂伊马替尼产生反应的致癌 Kit 信号驱动。在基线时，γδ T 细胞具有抗肿瘤作用，因为阻断 γδ TCR 或 IL17A 会增加肿瘤重量并降低抗肿瘤免疫力。然而，通过流式细胞术和单细胞 RNA 测序确定，伊马替尼疗法进一步刺激了瘤内 γδ T 细胞。伊马替尼扩增了高度活化的 γδ T 细胞亚群，增加了 IL17A 的产生以及免疫检查点和溶细胞效应分子的更高表达。与小鼠模型一致，γδ T 细胞在新鲜的人类 GIST 标本中产生 IL17A，并且通过大量肿瘤 RNA 测序测量，伊马替尼治疗增加了 γδ T 细胞基因特征。此外，肿瘤 γδ T 细胞与 GIST 患者的生存相关。我们的研究结果强调了肿瘤细胞癌基因信号传导与抗肿瘤免疫反应之间的相互作用，并将 γδ T 细胞确定为 GIST 免疫治疗的靶点。

γδ T cells are a rare but potent subset of T cells with pleiotropic functions. They commonly reside within tumors but the response of γδ T cells to tyrosine kinase inhibition is unknown. To address this, we studied a genetically engineered mouse model of gastrointestinal stromal tumor (GIST) driven by oncogenic Kit signaling that responds to the Kit inhibitor imatinib. At baseline, γδ T cells were anti-tumoral, as blockade of either γδ TCR or IL17A increased tumor weight and decreased antitumor immunity. However, imatinib therapy further stimulated intratumoral γδ T cells, as determined by flow cytometry and single-cell RNA sequencing. Imatinib expanded a highly activated γδ T-cell subset with increased IL17A production and higher expression of immune checkpoints and cytolytic effector molecules. Consistent with the mouse model, γδ T cells produced IL17A in fresh human GIST specimens, and imatinib treatment increased γδ T-cell gene signatures, as measured by bulk tumor RNA sequencing. Furthermore, tumor γδ T cells correlated with survival in GIST patients. Our findings highlight the interplay between tumor cell oncogene signaling and antitumor immune responses and identify γδ T cells as targets for immunotherapy in GIST.