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

Eur J Pharmacol. 2025 May 5:994:177367. doi: 10.1016/j.ejphar.2025.177367. Epub 2025 Feb 20.

Abstract

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.

Keywords: CD36; Obacunone; PD-1; Pancreatic cancer; immunotherapy.

MeSH terms

  • Animals
  • CD36 Antigens* / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Drug Synergism
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Mice
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / immunology
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / immunology
  • Signal Transduction / drug effects

Substances

  • Programmed Cell Death 1 Receptor
  • CD36 Antigens
  • Immune Checkpoint Inhibitors