γδT细胞(γδ)定居于人类组织，包括肿瘤内，但是他们在介导免疫检查点抑制的抗肿瘤反应中的功能还不清楚。我们展示了肾癌浸润了Vδ2-γδT细胞，其中等量代表Vδ1+和Vδ1-细胞，与在正常人类组织中发现的γδT细胞不同。这些定居于肿瘤内的Vδ2-细胞可以表达疲劳的αβ CD8+T细胞的转录程序，以及末级T细胞疲劳的经典标记，包括PD-1、TIGIT和TIM-3。虽然Vδ2-γδT细胞的IL-2产生减少，但他们保留了细胞毒性效应分子和共刺激受体，如4-1BB的表达。耗竭的Vδ2-γδT细胞由三个不同的人群组成，缺乏TCF7，在克隆扩张和多个Vδ2-T细胞受体表达细胞毒素分子方面表现出色。人类肿瘤来源的Vδ2-γδT细胞在体外保持细胞毒性功能和促炎性细胞因子的分泌。预处理肿瘤活检中Vδ2-T细胞的转录程序被用来预测患有癌症的患者对PD-1阻断的随后临床反应。因此，肿瘤微环境中的Vδ2-γδT细胞可以促进抗肿瘤效力。© 2023.作者（们）。

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2- γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2- γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2- T-cell receptors. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.© 2023. The Author(s).