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:10.1080/2162402X.2024.2326694

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

Oncoimmunology. 2024 Mar 12;13(1):2326694. doi: 10.1080/2162402X.2024.2326694. eCollection 2024.

Authors

Erin M Dickey¹, Anna Bianchi¹, Haleh Amirian¹, Peter J Hosein^{2

3}, Denise Faustman⁴, Roberta Brambilla⁵, Jashodeep Datta^{1

3}

Affiliations

¹ Division of Surgical Oncology, DeWitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
² Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
³ Sylvester Comprehensive Cancer Center, Miami, FL, USA.
⁴ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Abstract

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.

MeSH terms

Humans
Pancreatic Neoplasms*
Receptors, Tumor Necrosis Factor, Type II* / genetics
Signal Transduction
Tumor Necrosis Factor-alpha

Substances

Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha

Abstract

MeSH terms

Substances

Grants and funding