Evidence map›Paper›PMID 33592174›Full record

ArticleCell2021

Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis.

Nathan D Mathewson, Orr Ashenberg, Itay Tirosh, Simon Gritsch, Elizabeth M Perez, Sascha Marx, Livnat Jerby-Arnon, Rony Chanoch-Myers, Toshiro Hara, Alyssa R Richman and 30 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 298 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
298citing papers in PubMed, 1 pooled it
23.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

298 citing papers in PubMed, 1 synthesis or guideline pooled it, 387 citations in OpenAlex.

  1. Pooled it
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  3. Abundant CD8British journal of cancer · 2026
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238 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

40 authors at 8 institutions in 3 countries.

Nathan D MathewsonDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Orr AshenbergBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Itay TiroshDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
Simon GritschBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Elizabeth M PerezBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
Sascha MarxDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
Livnat Jerby-ArnonBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Rony Chanoch-MyersDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
Toshiro HaraBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Alyssa R RichmanBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Yoshinaga ItoDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
Jason PyrdolDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Mirco FriedrichDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Kathrin SchumannDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
Michael J PoitrasExperimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Prafulla C GokhaleExperimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
L Nicolas Gonzalez CastroDepartment of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Marni E ShoreBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Christine M HebertBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Brian ShawDepartments of Neurology and Radiation Oncology, Divisions of Hematology/Oncology and Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
Heather L CahillDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Matthew DrummondDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Wubing ZhangDepartment of Data Science, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Olamide OlawoyinDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hiroaki WakimotoDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
Orit Rozenblatt-RosenBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Genentech, South San Francisco, CA, USA.
Priscilla K BrastianosDepartments of Neurology and Radiation Oncology, Divisions of Hematology/Oncology and Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
X Shirley LiuDepartment of Data Science, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Pamela S JonesDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
Matthew P FroschDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
David N LouisDepartment of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Keith L LigonDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Alexander MarsonDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
E Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
David A ReardonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: david_reardon@dfci.harvard.edu.
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Genentech, South San Francisco, CA, USA; Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA 02139, USA. Electronic address: aregev@broadinstitute.org.
Mario L SuvàBroad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. Electronic address: suva.mario@mgh.harvard.edu.
Kai W WucherpfennigDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: kai_wucherpfennig@dfci.harvard.edu.
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · USMassachusetts General Hospital · USBrigham and Women's Hospital · USWeizmann Institute of Science · ILGladstone Institutes · USUniversity of California, San Francisco · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WENDY Beth LONDON · 2013 to 2026
$33.5M
Understanding and Overcoming T cell Immunosuppression in GlioblastomaP01CA236749 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI DAVID A REARDON · 2020 to 2026
$19.5M
Training Program in Nervous System TumorsK12CA090354 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PLOTKIN, SCOTT R · 2001 to 2025
$16.3M
Trinity: Transcriptome assembly for genetic and functional analysis of cancerU24CA180922 · NCI · BROAD INSTITUTE, INC. · PI HAAS, BRIAN · 2013 to 2022
$7.5M
Targeting the neuronal microenvironment in glioblastomaU19CA264504 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy T Batchelor · 2021 to 2026
$6.4M
Therapeutic Targeting of Immune Evasion from the MICA - NKG2D PathwayR01CA238039 · NCI · DANA-FARBER CANCER INST · PI Kai W Wucherpfennig · 2019 to 2026
$4.2M
Identification of genomic drivers of brain metastases in lung adenocarcinomaR01CA227156 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, CARTER, SCOTT · 2018 to 2022
$3.5M
Using MRI and circulating tumor DNA to improve the interpretation of response to immunotherapy and targeted therapy in CNS metastasesR01CA244975 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BRASTIANOS, PRISCILLA KALIOPI, GERSTNER, ELIZABETH · 2020 to 2024
$3.4M
Dissecting the cellular hierarchies of malignant gliomas by single-cell functional genomicsR37CA245523 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Mario Luca Suva · 2020 to 2026
$2.8M
Targeting Nicotinamide Adenine Dinucleotide (NAD+) metabolism in IDH mutant gliomasR01CA227821 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CAHILL, DANIEL P., WAKIMOTO, HIROAKI · 2018 to 2022
$2.4M
Targeting of a Major Immune Evasion Pathway in Triple-negative Breast CancerR01CA251599 · NCI · DANA-FARBER CANCER INST · PI WUCHERPFENNIG, KAI W · 2020 to 2024
$2.4M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA090354NCI NIH HHS L30 CA231679NCI NIH HHS P01 CA236749NCI NIH HHS P30 CA014051NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA227156NCI NIH HHS R01 CA227821NCI NIH HHS R01 CA234018NCI NIH HHS R01 CA238039NCI NIH HHS R01 CA244975NCI NIH HHS R01 CA251599NCI NIH HHS R21 CA220253NCI NIH HHS R33 CA202820NCI NIH HHS R37 CA245523NCI NIH HHS U19 CA264504NCI NIH HHS U24 CA180922
6 · The paper itself

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.

Indexed as

AnimalsAntigens, NeoplasmDisease Models, AnimalGene Expression ProfilingGliomaKiller Cells, NaturalLectins, C-TypeLymphocytes, Tumor-InfiltratingMiceNK Cell Lectin-Like Receptor Subfamily BReceptors, Cell SurfaceSingle-Cell AnalysisT-LymphocytesT-Lymphocyte SubsetsTumor EscapeAntigens, NeoplasmCLEC2D protein, humanKLRB1 protein, humanLectins, C-TypeNK Cell Lectin-Like Receptor Subfamily BReceptors, Cell SurfaceCD161glioblastomaIDH-mutant gliomassingle-cell RNA-seqT cells

Identifiers

PMID33592174
PMCPMC7935772
OpenAlexW3131460561

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.