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| Status |
Public on Apr 06, 2024 |
| Title |
ARID1A suppresses R-loop mediated STING-Type I Interferon pathway activation of anti-tumor immunity (scRNA/TCR-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Sorted on CD3+ CD8+ T cells and loaded into 10X ChIP K and processed with Chromium Next GEM Single Cell 5’ Reagent Kit v2 and TCR amplification kit.
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| Contributor(s) |
Maxwell M, Hargreaves D |
| Citation(s) |
38754421 |
| |
| Submission date |
Nov 11, 2022 |
| Last update date |
May 27, 2024 |
| Contact name |
Diana C. Hargreaves |
| E-mail(s) |
[email protected]
|
| Organization name |
The Salk Institute for Biological Studies
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| Street address |
10010 North Torrey Pines Road
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE217807 |
ARID1A suppresses R-loop mediated STING-Type I Interferon pathway activation of anti-tumor immunity |
|
| Relations |
| BioProject |
PRJNA900586 |
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