1. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis
- Author
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Mathewson, Nathan D, Ashenberg, Orr, Tirosh, Itay, Gritsch, Simon, Perez, Elizabeth M, Marx, Sascha, Jerby-Arnon, Livnat, Chanoch-Myers, Rony, Hara, Toshiro, Richman, Alyssa R, Ito, Yoshinaga, Pyrdol, Jason, Friedrich, Mirco, Schumann, Kathrin, Poitras, Michael J, Gokhale, Prafulla C, Gonzalez Castro, L Nicolas, Shore, Marni E, Hebert, Christine M, Shaw, Brian, Cahill, Heather L, Drummond, Matthew, Zhang, Wubing, Olawoyin, Olamide, Wakimoto, Hiroaki, Rozenblatt-Rosen, Orit, Brastianos, Priscilla K, Liu, X Shirley, Jones, Pamela S, Cahill, Daniel P, Frosch, Matthew P, Louis, David N, Freeman, Gordon J, Ligon, Keith L, Marson, Alexander, Chiocca, E Antonio, Reardon, David A, Regev, Aviv, Suvà, Mario L, and Wucherpfennig, Kai W
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Rare Diseases ,Immunization ,Cancer ,Genetics ,Vaccine Related ,Brain Disorders ,Stem Cell Research ,Neurosciences ,Brain Cancer ,Human Genome ,Stem Cell Research - Nonembryonic - Human ,Animals ,Antigens ,Neoplasm ,Disease Models ,Animal ,Gene Expression Profiling ,Glioma ,Killer Cells ,Natural ,Lectins ,C-Type ,Lymphocytes ,Tumor-Infiltrating ,Mice ,NK Cell Lectin-Like Receptor Subfamily B ,Receptors ,Cell Surface ,Single-Cell Analysis ,T-Lymphocyte Subsets ,T-Lymphocytes ,Tumor Escape ,CD161 ,IDH-mutant gliomas ,T cells ,glioblastoma ,single-cell RNA-seq ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.
- Published
- 2021