Obacunone potentiated PD-1 immunotherapy in pancreatic cancer by mediating CD36

Chemotherapy for patients with pancreatic cancer typically has a poor prognosis. Immunotherapy is currently a hot therapeutical approach to treat tumors. Various studies have shown that natural products have numerous activities, especially in the anti-tumor field. The triterpenoid class compound Obacunone has been shown to have various bioactivities, including anti-cancer properties. In this study, combining Obacunone with anti-PD-1 to treat pancreatic cancer in mice enhanced the anti-cancer activity of anti-PD-1 and suppressed tumor growth significantly. Proteomic analysis, immunofluorescence, Western blot, and flow cytometry revealed that this combination of compounds modulated the CD36-mediated PPAR signaling pathway to improve the infiltration and number of immune-associated CD4⁺ and CD8⁺ T cells in tumors. This report provides a new strategy for discovering immunotherapy for pancreatic cancer.