| Literature DB >> 33592174 |
Nathan D Mathewson1, Orr Ashenberg2, Itay Tirosh3, Simon Gritsch4, Elizabeth M Perez5, Sascha Marx6, Livnat Jerby-Arnon7, Rony Chanoch-Myers3, Toshiro Hara4, Alyssa R Richman4, Yoshinaga Ito6, Jason Pyrdol8, Mirco Friedrich8, Kathrin Schumann9, Michael J Poitras10, Prafulla C Gokhale10, L Nicolas Gonzalez Castro11, Marni E Shore4, Christine M Hebert4, Brian Shaw12, Heather L Cahill13, Matthew Drummond13, Wubing Zhang14, Olamide Olawoyin8, Hiroaki Wakimoto15, Orit Rozenblatt-Rosen16, Priscilla K Brastianos12, X Shirley Liu14, Pamela S Jones15, Daniel P Cahill15, Matthew P Frosch13, David N Louis13, Gordon J Freeman17, Keith L Ligon18, Alexander Marson19, E Antonio Chiocca20, David A Reardon21, Aviv Regev22, Mario L Suvà23, Kai W Wucherpfennig24.
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.Entities:
Keywords: CD161; IDH-mutant gliomas; T cells; glioblastoma; single-cell RNA-seq
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Year: 2021 PMID： 33592174 PMCID： PMC7935772 DOI： 10.1016/j.cell.2021.01.022
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 66.850