Evidence map›Paper›PMID 38754421›Full record

ArticleCell2024

ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity.

Matthew B Maxwell, Marianne S Hom-Tedla, Jawoon Yi, Shitian Li, Samuel A Rivera, Jingting Yu, Mannix J Burns, Helen M McRae, Braden T Stevenson, Katherine E Coakley and 9 more

Abstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
–field-weighted citation impact
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

92 citing papers in PubMed.

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  18. Loss of ARID1A expression is associated with worse survival and reduced tumor infiltrating lymphocytes in advanced clear cell renal cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Matthew B MaxwellMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92092, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Marianne S Hom-TedlaMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Gynecologic Oncology, University of California, San Diego, San Diego, CA, USA.
Jawoon YiMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Shitian LiMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92092, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Samuel A RiveraMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Biological Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92092, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jingting YuIntegrative Genomics and Bioinformatics Core, Salk Institute of Biological Studies, La Jolla, CA 92037, USA.
Mannix J BurnsMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Helen M McRaeMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Braden T StevensonMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Katherine E CoakleyMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Gynecologic Oncology, University of California, San Diego, San Diego, CA, USA.
Josephine HoMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Kameneff Bojorquez GastelumMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Joshua C BellMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Alexander C JonesMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Ramez N EskanderCenter for Personalized Cancer Therapy and Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, UC San Diego Moores Cancer Center, La Jolla, CA, USA.
Emily C DykhuizenDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Gerald S ShadelMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Susan M KaechNOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Diana C HargreavesMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: dhargreaves@salk.edu.

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Regulation of memory CD8 T cell developmentR01AI066232 · NIAID · YALE UNIVERSITY · PI Diana Clare Hargreaves · 2005 to 2026
$5.7M
(PQ5) Mitochondrial Heterogeneity in Melanoma Tumor and Immune ResponsesR01CA216101 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GERALD SHADEL · 2018 to 2026
$5.0M
MOLECULAR BIOLOGICAL APPROACHES TO ENDOCRINOLOGYT32DK007541 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAULTON, KYLE JEFFRIE, MAJITHIA, AMIT · 1987 to 2022
$4.5M
Understanding how metabolic heterogeneity in cancer affects the tumor microenvironment and anti-tumor immunityR01CA240909 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI KAECH, SUSAN M · 2020 to 2024
$3.0M
Mitochondria-to-Nucleus Signaling in Colorectal CancerR01CA228211 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI HARGREAVES, DIANA CLARE, SHADEL, GERALD · 2020 to 2024
$2.6M
The Role of the Tumor Suppressor ARID1A in R loop Homeostasis and Tumor ImmunityR01CA285867 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Diana Clare Hargreaves · 2024 to 2026
$1.7M
BD FACSAria Fusion for Flow Cytometry Core FacilityS10OD023689 · OD · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI ZHENG, YE · 2018 to 2018
$530k
BAF complex inhibitors in neuronal development and functionsR21MH128678 · NIMH · UNIVERSITY OF CALIFORNIA, MERCED · PI DYKHUIZEN, EMILY CARLA, SAHA, RAMENDRA N · 2022 to 2023
$433k
NCI NIH HHS P30 CA014195NCI NIH HHS R01 CA216101NCI NIH HHS R01 CA228211NCI NIH HHS R01 CA240909NCI NIH HHS R01 CA285867NIAID NIH HHS R01 AI066232NIDDK NIH HHS T32 DK007541NIH HHS S10 OD023689NIMH NIH HHS R21 MH128678
6 · The paper itself

Abstract

Clinical trials have identified ARID1A mutations as enriched among patients who respond favorably to immune checkpoint blockade (ICB) in several solid tumor types independent of microsatellite instability. We show that ARID1A loss in murine models is sufficient to induce anti-tumor immune phenotypes observed in ARID1A mutant human cancers, including increased CD8+ T cell infiltration and cytolytic activity. ARID1A-deficient cancers upregulated an interferon (IFN) gene expression signature, the ARID1A-IFN signature, associated with increased R-loops and cytosolic single-stranded DNA (ssDNA). Overexpression of the R-loop resolving enzyme, RNASEH2B, or cytosolic DNase, TREX1, in ARID1A-deficient cells prevented cytosolic ssDNA accumulation and ARID1A-IFN gene upregulation. Further, the ARID1A-IFN signature and anti-tumor immunity were driven by STING-dependent type I IFN signaling, which was required for improved responsiveness of ARID1A mutant tumors to ICB treatment. These findings define a molecular mechanism underlying anti-tumor immunity in ARID1A mutant cancers.

Indexed as

CD8-Positive T-LymphocytesDNA-Binding ProteinsInterferon Type IMembrane ProteinsNeoplasmsSignal TransductionTranscription FactorsAnimalsCell Line, TumorChemokinesExodeoxyribonucleasesHumansImmune Checkpoint InhibitorsMaleMiceMice, Inbred C57BLARID1A protein, humanArid1a protein, mouseChemokinesDNA-Binding ProteinsExodeoxyribonucleasesImmune Checkpoint InhibitorsInterferon Type IMembrane ProteinsNuclear ProteinsPhosphoproteinsSTING1 protein, humanSting1 protein, mouseSTING Proteinthree prime repair exonuclease 1Transcription Factorsanti-tumor immunityARID1Acancer immunotherapycytosolic DNAR-loopsSTINGSWI/SNF complextype I IFN

Identifiers

PMID38754421
PMCPMC11193641

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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.