Pancreatic cancer is characterized by extreme therapeutic resistance. In pancreatic cancers harboring high-risk genomes, we describe that cancer cell-neutrophil signaling circuitry provokes neutrophil-derived transmembrane (tm)TNF-TNFR2 interactions that dictate inflammatory polarization in cancer-associated fibroblasts and T-cell dysfunction - two hallmarks of therapeutic resistance. Targeting tmTNF-TNFR2 signaling may sensitize pancreatic cancer to chemo±immunotherapy.
Keywords: Chemotherapy; TNFR2; immunotherapy; myeloid-derived suppressor cells; neutrophils; pancreatic cancer; tumor necrosis factor.
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.