Stromal HIF2 Regulates Immune Suppression in the Pancreatic Cancer Microenvironment.

ABSTRACT:

Background & aims

Pancreatic ductal adenocarcinoma (PDAC) has a hypoxic, immunosuppressive stroma that contributes to its resistance to immune checkpoint blockade therapies. The hypoxia-inducible factors (HIFs) mediate the cellular response to hypoxia, but their role within the PDAC tumor microenvironment remains unknown.

Methods

We used a dual recombinase mouse model to delete Hif1α or Hif2α in α-smooth muscle actin-expressing cancer-associated fibroblasts (CAFs) arising within spontaneous pancreatic tumors. The effects of CAF HIF2α expression on tumor progression and composition of the tumor microenvironment were evaluated by Kaplan-Meier analysis, reverse transcription quantitative real-time polymerase chain reaction, histology, immunostaining, and by both bulk and single

SUBMITTER: Garcia Garcia CJ 

PROVIDER: S-EPMC9278556 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature