The TGF-βR1 inhibitor galunisertib re-shapes the PDAC-TME by limiting decidual-like natural killer cells polarization - PubMed
4 hours ago
- #Immunotherapy
- #NK Cells
- #Pancreatic Cancer
- Galunisertib (GAL), a TGF-βR1 inhibitor, reshapes the PDAC tumor microenvironment by reducing decidual-like natural killer (NK) cell polarization.
- PDAC patients show elevated TGF-β1/TGF-βR1 levels, linked to worse outcomes, and have expanded CD9+ NK cells with pro-angiogenic properties.
- PDAC cells and cancer-associated fibroblasts induce a CD9+ decidual-like phenotype in NK cells, impairing their cytotoxicity; GAL reverses this dysfunction.
- GAL downregulates the release of pro-tumor factors like FGF2, HGF, IL11, PLGF, EGFR, and VEGF from PDAC cells and fibroblasts.
- In vivo, GAL treatment reduces tumor weight, fibrosis, and angiogenesis, while promoting M1 macrophage polarization and activating NK and CD8+ T cells.