Dual Stromal Targeting Sensitizes Pancreatic Adenocarcinoma for Anti-Programmed Cell Death Protein 1 Therapy.

ABSTRACT:

Background & aims

The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.

Methods

A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations.

Results

The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi

SUBMITTER: Blair AB 

PROVIDER: S-EPMC9613523 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature