Combination of Ginsenoside Compound K and Anti-PD1 Inhibits Pancreatic Cancer by Activating CXCL13-CXCR5 Signaling Axis

Pancreatic cancer is a highly malignant tumor with a poor prognosis, making it a leading cause of cancer-related deaths. While immune checkpoint inhibitors (ICIs) have shown efficacy in treating various solid tumors, their effectiveness in pancreatic cancer is limited due to its unique tumor immune microenvironment (TIME). Thus, developing novel combination therapies is critical. Ginsenoside compound K (CK), a natural product with antitumor and immunomodulatory properties, holds the potential for combination therapy with ICIs. This study investigates the therapeutic effects of CK combined with Anti-PD1 inhibitors in a Panc02 tumor model. The combination therapy significantly improved survival, enhanced T-cell infiltration and activation, remodeled the tumor stroma by reducing collagen I and α-SMA, and improved vasculature formation. RNA sequencing revealed changes in genes associated with T-cell activation, chemokines, and angiogenesis. These findings suggest that CK combined with Anti-PD1 therapy offers a promising strategy for pancreatic cancer treatment by modulating TIME and enhancing antitumor activity.