Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis
© 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...
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| Format: | Article |
| Language: | English |
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Elsevier BV
2022
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| Online Access: | https://hdl.handle.net/1721.1/141418.2 |
| _version_ | 1811074199610982400 |
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| author | Regev, Aviv |
| author2 | Howard Hughes Medical Institute |
| author_facet | Howard Hughes Medical Institute Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T09:45:32Z |
| format | Article |
| id | mit-1721.1/141418.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:45:32Z |
| publishDate | 2022 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/141418.22022-10-12T13:57:53Z Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis Regev, Aviv Howard Hughes Medical Institute Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Biology © 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. 2022-10-12T13:57:52Z 2022-03-30T17:44:05Z 2022-10-12T13:57:52Z 2021 2022-03-30T17:38:28Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141418.2 2021. "Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis." Cell, 184 (5). en 10.1016/J.CELL.2021.01.022 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/octet-stream Elsevier BV PMC |
| spellingShingle | Regev, Aviv Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title | Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title_full | Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title_fullStr | Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title_full_unstemmed | Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title_short | Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis |
| title_sort | inhibitory cd161 receptor identified in glioma infiltrating t cells by single cell analysis |
| url | https://hdl.handle.net/1721.1/141418.2 |
| work_keys_str_mv | AT regevaviv inhibitorycd161receptoridentifiedingliomainfiltratingtcellsbysinglecellanalysis |