{"doi":"10.1016/j.cell.2021.01.022","title":"Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis","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.","journal":"Cell","year":2021,"id":2613,"datarank":0.8968328647351684,"base_score":5.978885764901122,"endowment":5.978885764901122,"self_citation_contribution":0.8968328647351684,"citation_network_contribution":0.0,"self_endowment_contribution":0.8968328647351684,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":394,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0542,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-03-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2691,"name":"Orr Ashenberg","orcid":"0000-0002-7802-8834","position":1,"is_corresponding":false},{"id":2735,"name":"Itay Tirosh","orcid":"0000-0001-5477-2987","position":2,"is_corresponding":false},{"id":2728,"name":"Simon Gritsch","orcid":"0000-0001-5682-5712","position":3,"is_corresponding":false},{"id":30760,"name":"Elizabeth M. 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