Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma

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Barilla, Rocky M
Diskin, Brian
Caso, Raul Caso
Lee, Ki Buom
Mohan, Navyatha
Buttar, Chandan
Adam, Salma
Sekendiz, Zennur
Wang, Junjie
Salas, Ruben D

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<jats:title>Abstract</jats:title><jats:p>The drivers and the specification of CD4<jats:sup>+</jats:sup> 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<jats:sub>H</jats:sub>-program. Specifically, CD11b<jats:sup>+</jats:sup>CD103<jats:sup>−</jats:sup> DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3<jats:sup><jats:italic>neg</jats:italic></jats:sup> tumor-promoting IL-10<jats:sup>+</jats:sup>IL-17<jats:sup>+</jats:sup>IFNγ<jats:sup>+ </jats:sup>regulatory CD4<jats:sup>+</jats:sup> T cells. The balance between this distinctive T<jats:sub>H</jats:sub> program and canonical FoxP3<jats:sup>+ </jats:sup>T<jats:sub>REGS</jats:sub> is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T<jats:sub>H</jats:sub>-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b<jats:sup>+</jats:sup>CD103<jats:sup>−</jats:sup> DC promote CD4<jats:sup>+</jats:sup> T cell tolerance in PDA which may underscore its resistance to immunotherapy.</jats:p>

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10.1038/s41467-019-09416-2

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Barilla, Rocky M, Brian Diskin, Raul Caso Caso, Ki Buom Lee, Navyatha Mohan, Chandan Buttar, Salma Adam, Zennur Sekendiz, et al. (n.d.). Specialized dendritic cells induce tumor-promoting IL-10+IL-17+ FoxP3neg regulatory CD4+ T cells in pancreatic carcinoma. Nature Communications, 10(1). 10.1038/s41467-019-09416-2 Retrieved from https://hdl.handle.net/10161/30185.

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