The Aging Microenvironment as a Determinant of Immune Exclusion and Metastatic Fate in Pancreatic Cancer.

ABSTRACT: Aging is a critical yet understudied determinant in pancreatic ductal adenocarcinoma (PDAC). Despite a strong epidemiological association with age, conventional PDAC preclinical models fail to capture the histopathological and stromal complexities that emerge in older organisms. Using an age-relevant syngeneic orthotopic model, we demonstrate that organismal aging accelerates PDAC progression and metastasis. Through transcriptomic profiling, we identify a conserved extracellular matrix gene signature enriched in cancer-associated fibroblasts (CAFs) from aged tumors, consistent with an augmented fibrotic landscape that supports immunosuppression, metastatic tropism, and poor prognosis. To directly test the functional impact of stromal aging, we employed heterochronic co-implantation models,

SUBMITTER: Gupta P 

PROVIDER: S-EPMC12248120 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature