IMMUNOLOGY2025™ Conference Recordings-BAF complexes and tumor immunity

Video Transcription

Video Summary

The speaker described how the BAF chromatin remodeling complex controls gene accessibility and is essential for development, differentiation, and immune cell function. Focusing on the ARID1A subunit, frequently mutated in many cancers, they explained that ARID1A mutations are associated with better responses to immune checkpoint blockade in patients.<br /><br />Using mouse melanoma and colon cancer models, the lab showed that ARID1A loss reduced tumor growth and increased infiltration and activation of immune cells, especially CD8 T cells. Mechanistically, ARID1A deficiency caused accumulation of R-loops and cytosolic nucleic acids, triggering cGAS-STING and type I interferon signaling, which induced interferon-stimulated genes and enhanced tumor immunogenicity. Blocking type I interferon or removing T/B cells reversed this effect.<br /><br />The talk then extended these findings to pharmacologic BAF inhibition. A BAF inhibitor combined with anti-PD-L1 strongly suppressed tumor growth and induced interferon-related programs in both tumor and immune cells. A major effect was seen in tumor-associated macrophages, which were reprogrammed toward a more anti-tumor state with increased MHC class I and CD86, ultimately boosting CD8 T cell activity. Overall, BAF inhibition may improve immunotherapy by converting cold tumors into inflamed, immune-responsive tumors.

Keywords

BAF chromatin remodeling

ARID1A mutation

immune checkpoint blockade

CD8 T cells

cGAS-STING signaling

type I interferon

BAF inhibitor