Genomic instability drives POSTN+ myofibroblasts via STING-WNT axis to promote immunosuppression and PARPi resistance in ovarian cancer - PubMed
3 hours ago
- #genomic instability
- #immunosuppression
- #PARP inhibitor resistance
- Genomic instability in ovarian cancer activates tumor-intrinsic STING signaling, leading to secretion of WNT3a/7a.
- WNT/β-catenin signaling in fibroblasts establishes a POSTN+ myofibroblast-like CAF lineage through a positive feedback loop, epigenetically locking cells.
- POSTN+ myCAFs promote immunosuppression by expanding regulatory T cells and exhausting CD8+ T cells.
- This stromal reprogramming converts genomic instability-driven immune activation into suppression and contributes to PARP inhibitor resistance.
- Therapeutic blockade of POSTN reinvigorates T cell cytotoxicity, depletes regulatory T cells, and enhances PARP inhibition in cancer models.