小柯机器人

美国加州大学Lawrence Fong团队近期取得重要工作进展，他们研究发现人肾癌中耗竭的瘤内Vδ2⁻ γδ T细胞保留效应功能。相关研究成果2023年3月16日在线发表于《自然—免疫学》杂志上。

据介绍，γδ T细胞存在于包括肿瘤在内的人类组织中，但它们在介导免疫检查点抑制的抗肿瘤反应中的功能尚不清楚。

研究人员发现肾癌被Vδ2⁻γδ T细胞浸润，Vδ1⁺和Vδ1⁻细胞的表达相当，这与正常人体组织中发现的γδ T淋巴细胞不同。这些肿瘤驻留的Vδ2⁻ T细胞可以表达耗竭的αβ CD8⁺ T细胞的转录程序，以及末端T细胞耗竭的经典标志物（包括PD-1、TIGIT和TIM-3）。尽管Vδ2⁻ γδT细胞减少了IL-2的产生，但它们保留了溶解效应分子和共刺激受体（如4-1BB）的表达。耗竭的Vδ2⁻ γδT细胞由三个不同的群体组成，这些群体缺乏TCF7，克隆扩增并表达细胞毒性分子和多种Vδ2^– T细胞受体。人类肿瘤来源的Vδ2⁻ γδ T细胞在体外维持细胞毒性功能和促炎细胞因子分泌。预处理肿瘤活检中Vδ2⁻ T细胞的转录程序用于预测癌症患者对PD-1阻断的后续临床反应。

总之，这一研究表明肿瘤微环境中的Vδ2⁻ γδ T细胞可以促进抗肿瘤疗效。

附：英文原文

Title: Exhausted intratumoral Vδ2− γδ T cells in human kidney cancer retain effector function

Author: Rancan, Chiara, Arias-Badia, Marcel, Dogra, Pranay, Chen, Brandon, Aran, Dvir, Yang, Hai, Luong, Diamond, Ilano, Arielle, Li, Jacky, Chang, Hewitt, Kwek, Serena S., Zhang, Li, Lanier, Lewis L., Meng, Maxwell V., Farber, Donna L., Fong, Lawrence

Issue&Volume: 2023-03-16

Abstract: 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.

DOI: 10.1038/s41590-023-01448-7

Source: https://www.nature.com/articles/s41590-023-01448-7

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex