Journal
CELL
Volume 184, Issue 5, Pages 1281-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.01.022
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Funding
- Ben and Catherine Ivy Foundation
- Bridge Project
- Koch Institute for Integrative Cancer Research at MIT
- DanaFarber/Harvard Cancer Center
- NIH [R01CA227821, P50CA165962]
- Ambrose Monell Foundation
- MGH Research Scholars
- Sontag Foundation
- Zuckerman STEM Leadership Program
- Human Frontier Science Program
- Mexican Friends New Generation
- Benoziyo Endowment Fund for the Advancement of Science
- Parker Institute for Cancer Immunotherapy (PICI)
- American Cancer Society [PF-17-042-01-LIB]
- NIH education loan repayment program - NCI [L30 CA231679-01]
- Deutsche Forschungsgemeinschaft (DFG) [GR 5252/1-1]
- Burroughs Wellcome Fund
- Cancer Research Institute (CRI) Lloyd J. Old STAR award
- Innovative Genomics Institute (IGI)
- Howard Hughes Medical Institute
- Klarman Cell Observatory, NCI [1U24CA180922, R33CA202820, P30-CA14051]
- National Cancer Institute
- Ludwig Center at MIT
- National Science Foundation Graduate Research Fellowship [DGE1745303]
- Burroughs Wellcome Fund (BWF)
- Wendy Schmidt postdoctoral program
- K12 award [CA090354]
- Loglio Foundation
- Japan Society for the Promotion of Science, SENSHIN Medical Research Foundation
- Kanae Foundation for the Promotion of Medical Science
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This study utilized single-cell RNA sequencing to uncover the gene expression and clonal landscape of T cells in diffuse gliomas, identifying potential effectors of anti-tumor immunity. The research revealed that KLRB1 and its associated transcriptional program play an inhibitory role in tumor immunity, and blocking its function enhances T cell killing of glioma cells.
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.
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