Fig. 1: Senescence creates therapeutic liabilities for chemo- and immunotherapy in PDAC.
From: Combating pancreatic cancer during its Rip Van Winkle sleep
Trametinib (T) and palbociclib (P) combo treatment induces SASP factors, which enhance vascular remodeling and decrease hyaluronic acid texture without affecting collagen deposition in TME. Vascular remodeling in PDAC allows increased vascular perfusion, causing enhanced gemcitabine delivery. At the same time, increased vessel density and endothelial cell activation permits escalated CD8+ T cell infiltration. Combo treatment-induced SASP factors boost T cell activation and exhaustion, enabling PD-1/PD-L1 axis susceptible to immunotherapy.
