Myofibroblast programming blocks differentiation of TLS-organizing fibroblastic reticular cells in pancreatic cancer - PubMed
3 hours ago
- #pancreatic cancer
- #fibroblasts
- #TLS
- Myofibroblast programming inhibits differentiation of TLS-organizing fibroblastic reticular cells in pancreatic cancer, affecting immunotherapy response.
- TLS formation in PDAC is linked to improved survival; TLS-permissive models have reticular-CAFs (rCAFs), while resistant models show myofibroblastic CAFs (myCAFs).
- LTBR agonist induces TLS in some PDAC models, but myCAF blocks chemokine upregulation and lymphocyte migration, hindering TLS formation.
- Combining TGFβ receptor inhibition with LTBR agonism promotes TLS formation and T cell-dependent tumor control in PDAC.
- In patient tumors, rCAFs are near TLS, while myCAFs are distal, suggesting myCAF repression of rCAF programming can be therapeutically targeted.