The Crosstalk with CXCL10‐Rich Tumor‐Associated Mast Cells Fuels Pancreatic Cancer Progression and Immune Escape

• DOI: 10.1002/advs.202417724
• Publication Date: 2025-02-18T18:50:36Z
• Authors: Hanlin Yin; Qiangda Chen; Shanshan Gao; Sami Shoucair; Yuqi Xie; Joseph R. Habib; Taochen He; Wei Gan; Juan Wang; Lei Zhang; Huaxiang Xu; Chenye Shi; Junyi He; Wenquan Wang; Yun Jin; Michael G Goggins; Liang Liu; Wenhui Lou; Wenchuan Wu; Jun Yu; Ning Pu
• Keywords: Tumor progression; CXCR3

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, necessitating approaches to improve prognosis. As the mediator of allergic process, mast cells have been found in various cancers and are associated with survival. However, biological behaviors tumor‐associated (TAMCs) remain unclear. Herein, an excessive infiltration TAMCs PDAC demonstrated, which apparently poor survival patients. recruit CXCR2 + MCs into TME, then inhibited ferroptosis, maintained their proliferation. Concomitantly, tumor‐derived exosome miR‐188‐5p activated PTEN/AKT/GSK3β signaling, further stabilized transcriptional factor ERG by inhibiting its ubiquitin degradation, finally enhanced transcription cxcl10 within TAMCs. In reverse, TAMCs‐derived CXCL10 reversely promoted tumor epithelial‐mesenchymal transition induced immunosuppressive microenvironment recruiting CXCR3 Tregs. Sodium cromoglycate (SCG) membrane stabilizer for confirmed as effective widely used agent block sensitize therapeutic efficacy anti‐PD‐1 antibody plus gemcitabine PDAC. These findings illuminate critical innovative crosstalk between that promote progression, SCG sensitizes current immuno‐chemotherapy, reveals potential be valuable adjuvant