1. 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., and Fong, Lawrence
- 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.
- Published
- 2023
- Full Text
- View/download PDF