PPY-Induced iCAFs Cultivate an Immunosuppressive Microenvironment in Pancreatic Cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by cancer cells surrounded by affluent stromal components, which may underlie their limited response to various therapeutic interventions, including immunotherapy. Inflammatory cancer-associated fibroblasts (iCAFs), a crucial subset of CAFs within the PDAC microenvironment, play a pivotal role in shaping an immunosuppressive microenvironment. In this study, single-cell RNA sequencing analysis is performed to screen for cancer cells-secreted proteins associated with iCAF induction, and PPY (pancreatic polypeptide) is validated as a potent inducer. Unlike previously reported iCAF inducers, PPY is a gastrointestinal hormone predominantly expressed in the pancreas, suggesting that targeting it may have minimal systemic effects. Multiplex

SUBMITTER: Cao M 

PROVIDER: S-EPMC12120788 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature