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

ABSTRACT: Aging is a critical yet understudied determinant in pancreatic ductal adenocarcinoma (PDAC) risk and outcomes. Despite a strong epidemiologic association with age, conventional PDAC preclinical models fail to capture the histopathologic and stromal complexities that emerge in older organisms. Using an age-relevant syngeneic orthotopic model, we demonstrated that organismal aging accelerates PDAC progression and metastasis. Transcriptomic and secretome profiling identified a conserved extracellular matrix gene signature enriched in cancer-associated fibroblasts (CAF) from aged tumors, consistent with an augmented fibrotic landscape that supports immunosuppression, metastatic tropism, and poor prognosis. Direct testing of the functional impact of stromal aging in heterochronic co-implantatio

SUBMITTER: Gupta P 

PROVIDER: S-EPMC12768431 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature