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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.
Pubmed ID: 33592174 RIS Download
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A collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsSoftware application for recovery of T cell receptor (TCR) data from single cell data. Used to reconstruct full-length, paired T cell receptor (TCR) sequences from T lymphocyte single-cell RNA sequence data. Links T cell specificity with functional response by revealing clonal relationships between cells alongside their transcriptional profiles.
View all literature mentionsCell line Jurkat is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets CD16/32
View all literature mentionsThis monoclonal targets I-A/I-E
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View all literature mentionsThis monoclonal targets CD4
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View all literature mentionsThis monoclonal targets CD161
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View all literature mentionsThis monoclonal targets TCR Valpha7.2
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View all literature mentionsThis recombinant monoclonal targets CD159c (NKG2C)
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View all literature mentionsThis monoclonal targets CD8a
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View all literature mentionsThis monoclonal targets CD66b
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View all literature mentionsCell line J.RT3-T3.5 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
Cell line GL261-luc2 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line Jurkat E6.1 is a Cancer cell line with a species of origin Homo sapiens (Human)
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