Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis.

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; Wucherpfennig, Kai W     «

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...     »

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.      «

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 natur...     »