Specialized dendritic cells induce tumor-promoting IL-10IL-17 FoxP3 regulatory CD4 T cells in pancreatic carcinoma.

The drivers and the specification of CD4 T cell differentiation in the tumor microenvironment and their contributions to tumor immunity or tolerance are incompletely understood. Using models of pancreatic ductal adenocarcinoma (PDA), we show that a distinct subset of tumor-infiltrating dendritic cells (DC) promotes PDA growth by directing a unique T-program. Specifically, CD11bCD103 DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 tumor-promoting IL-10IL-17IFNγregulatory CD4 T cells. The balance between this distinctive T program and canonical FoxP3T is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11bCD103 DC promote CD4 T cell tolerance in PDA which may underscore its resistance to immunotherapy.