Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis
Name
nihms-1666011.pdf
Description
Accepted version
Size
3.55 MB
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Unknown
Checksum (MD5)
cfcef0ed2bd87f0b3d4749c6a27f4039
Author(s)
Regev, Aviv
Date Issued
2021
Journal
Cell
Publisher
Elsevier BV
Citation
2021. "Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis." Cell, 184 (5).
Version
Author's final manuscript
Abstract
© 2021 Elsevier Inc. 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. Single-cell analysis of tumor-infiltrating T cells in glioma patients identifies a T cell population co-expressing a cytotoxicity program and NK cell receptors. Mathewson et al. reveal the functional significance of NK cell receptors such as CD161 in inhibiting the anti-tumor function of T cells, highlighting their potential as targets for immunotherapy.
MIT Department
Howard Hughes Medical Institute
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2021.01.022
