Targeting Mast Cell Activation and MIF-Mediated Remodelling Enhances Chemotherapy Response in Pancreatic Cancer.

ABSTRACT: Neoadjuvant gemcitabine plus nab-paclitaxel (AG) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC), yet its effects on the tumor microenvironment (TME) remain incompletely defined. By integrating eight single-cell RNA sequencing datasets and nine multicenter transcriptomic cohorts, the dual impact of AG in PDAC is delineated. AG shifts residual malignant cells from basal toward a more indolent classical phenotype and remodels the TME into a more heterogeneous and intricate landscape. Specifically, AG activates tumor-associated mast cells (TAMCs), reprogrammes myofibroblastic cancer-associated fibroblasts (myCAFs) into inflammatory CAFs (iCAFs), and enhances suppressive crosstalk between TAMCs, iCAFs, and T cells via the macrophage migration inhibitory factor (MIF) axis. Co

SUBMITTER: Wang L 

PROVIDER: S-EPMC12752552 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature