OncoImmunology (Dec 2024)

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

DOI
https://doi.org/10.1080/2162402X.2024.2326694
Journal volume & issue
Vol. 13, no. 1

Abstract

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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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