Dynamic crosstalk between tumor-associated macrophages and cancer-associated fibroblasts in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis, with current therapeutic approaches demonstrating suboptimal efficacy. The development of novel treatment strategies or combination therapies to improve clinical outcomes is therefore imperative. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) serve as pivotal regulators in PDAC progression. These cell populations establish a positive feedback loop through both direct and indirect interactions, contributing significantly to stromal desmoplasia, the formation of a tumor immunosuppressive microenvironment (TIME), and the development of treatment resistance. The underlying interaction mechanisms may offer promising therapeutic targets for PDAC patients. This review presents the first comprehensive summary of the bidirectional interaction mechanisms between TAMs and CAFs in PDAC. Building upon existing research, we comprehensively elucidate recent advances in understanding these mechanisms and discuss emerging therapeutic strategies targeting these interactions. Furthermore, we propose anticipated future research directions, aiming to provide novel insights into PDAC progression and identify potential therapeutic avenues.