ARID1A Mediates SWI/SNF-Independent Maintenance of Heterochromatin Architecture to Restrain Viral Mimicry and Immunogenicity in Colon Cancer - PubMed
3 months ago
- #heterochromatin
- #ARID1A
- #immunotherapy
- ARID1A, a subunit of the SWI/SNF complex, has a SWI/SNF-independent role in maintaining heterochromatin architecture to suppress viral mimicry and immunogenicity in colorectal cancer.
- Loss of ARID1A disrupts heterochromatin stability by displacing SETDB1 from the TRIM28 complex, leading to reduced H3K9me3 repression at retroelements and triggering viral mimicry and type I interferon responses.
- Disrupting the ARID1A-TRIM28 interaction with synthetic peptides induces viral mimicry, converting 'cold' tumors into T-cell-inflamed microenvironments and enhancing sensitivity to PD-1 blockade.
- Both RNA and DNA cytosolic sensors are essential for the interferon response and improved immunotherapy outcomes in ARID1A-deficient tumors.