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Transmembrane TNF-TNFR2 signaling as a critical immunoregulatory node in pancreatic cancer.

Erin M Dickey, Anna Bianchi, Haleh Amirian, Peter J Hosein, Denise Faustman, Roberta Brambilla, Jashodeep Datta
Oncoimmunology 2024
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.

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