Aryl Hydrocarbon Receptor Ligands Drive Pancreatic Cancer Initiation and Progression through Protumorigenic T-cell Polarization.

ABSTRACT: Although smoking is a risk factor for pancreatic adenocarcinoma (PDAC), the underlying mechanisms promoting tumorigenesis and progression are unknown. In this study, we show that aryl hydrocarbon receptor (AHR) ligands found in cigarette smoke, like the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, promote pancreatic dysplasia and PDAC progression in a mouse model of this disease. This effect is mediated by AHR activation in CD4+ T cells, leading to their polarization to IL22-producing TH22 cells and regulatory T cell accumulation, ultimately driving a blunted CD8+ T-cell effector response. Analysis of human pancreata from organ donors revealed that smokers have increased AHR activation relative to nonsmokers. Similarly, PDAC tumors from patients with a history of cigarette smoking prese

SUBMITTER: Griffith BD 

PROVIDER: S-EPMC12793834 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature