Evidence map›Paper›PMID 35750052›Full record

ArticleCancer cell2022

Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence.

Julia A Belk, Winnie Yao, Nghi Ly, Katherine A Freitas, Yan-Ting Chen, Quanming Shi, Alfredo M Valencia, Eric Shifrut, Nupura Kale, Kathryn E Yost and 10 more

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

Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers.

0numbers the graph read from it
0cells of the map it votes in
239citing papers in PubMed
31.5field-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

239 citing papers in PubMed, 323 citations in OpenAlex.

  1. Trial
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  3. Article
  4. Review
  5. Targeting the CD4Molecular biomedicine · 2026
    Article
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  16. Review
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  18. Journal for immunotherapy of cancer · 2026
    Article
  19. Article
  20. Article

179 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 1 country.

Julia A BelkDepartment of Computer Science, Stanford University, Stanford, CA 94305, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
Winnie YaoDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Nghi LyDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Katherine A FreitasImmunology Graduate Program, Stanford University School of Medicine, Stanford, CA 94035, USA; Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94035, USA.
Yan-Ting ChenMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Quanming ShiDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Alfredo M ValenciaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
Eric ShifrutGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
Nupura KaleUCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Kathryn E YostCancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
Connor V DuffyDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Bence DanielGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Madeline A HweeMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Zhuang MiaoDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Alan AshworthUCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Crystal L MackallParker Institute of Cancer Immunotherapy, San Francisco, CA 94305, USA; Division of Pediatric Hematology/Oncology/Stem Cell Transplant and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94035, USA; Division of BMT and Cell Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94035, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Alexander MarsonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94305, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Julia CarnevaleGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Santosh A VardhanaMemorial Sloan Kettering Cancer Center, New York, NY, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94305, USA.
Ansuman T SatpathyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA 94035, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: satpathy@stanford.edu.
Stanford University · USGladstone Institutes · USMemorial Sloan Kettering Cancer Center · USUniversity of California, San Francisco · USNeurosciences Institute · USParker Institute for Cancer Immunotherapy · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
4DN Interrogation of T Cell Exhaustion in CancerU01CA260852 · NCI · STANFORD UNIVERSITY · PI SATPATHY, ANSUMAN · 2020 to 2024
$2.6M
Investigating altered T-cell metabolism during chronic antigen encounterK08CA237731 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI VARDHANA, SANTOSHA · 2020 to 2024
$1.3M
NCI NIH HHS K08 CA237731NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA108462NCI NIH HHS U01 CA260852
6 · The paper itself

Abstract

T cell exhaustion limits antitumor immunity, but the molecular determinants of this process remain poorly understood. Using a chronic stimulation assay, we performed genome-wide CRISPR-Cas9 screens to systematically discover regulators of T cell exhaustion, which identified an enrichment of epigenetic factors. In vivo CRISPR screens in murine and human tumor models demonstrated that perturbation of the INO80 and BAF chromatin remodeling complexes improved T cell persistence in tumors. In vivo Perturb-seq revealed distinct transcriptional roles of each complex and that depletion of canonical BAF complex members, including Arid1a, resulted in the maintenance of an effector program and downregulation of exhaustion-related genes in tumor-infiltrating T cells. Finally, Arid1a depletion limited the acquisition of exhaustion-associated chromatin accessibility and led to improved antitumor immunity. In summary, we provide an atlas of the genetic regulators of T cell exhaustion and demonstrate that modulation of epigenetic state can improve T cell responses in cancer immunotherapy.

Indexed as

Chromatin Assembly and DisassemblyNeoplasmsAnimalsChromatinEpigenomicsHumansMiceT-LymphocytesChromatincanonical BAF complexchromatin remodelingCRISPRepigeneticsgenomicsimmunologyin vivo Perturb-seqT cell exhaustion

Identifiers

PMID35750052
PMCPMC9949532
OpenAlexW4283328628

What OpenQuestion holds

Textmetadata
LicenceTDM
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.