1. Exhausted intratumoral Vδ2− γδ T cells in human kidney cancer retain effector function
- Author
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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
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Immunology ,Oncology and Carcinogenesis ,Kidney Disease ,Breast Cancer ,Clinical Research ,Cancer ,Underpinning research ,1.1 Normal biological development and functioning ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Good Health and Well Being ,Humans ,CD8-Positive T-Lymphocytes ,Receptors ,Antigen ,T-Cell ,gamma-delta ,Programmed Cell Death 1 Receptor ,Kidney Neoplasms ,T-Lymphocyte Subsets ,Tumor Microenvironment ,Biochemistry and cell biology - 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