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 H -program. Specifically, CD11b + CD103 − DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3 neg tumor-promoting IL-10 + IL-17 + IFNγ + regulatory CD4 + T cells. The balance between this distinctive T H program and canonical FoxP3 + T REGS is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T H -signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b + CD103 − DC promote CD4 + T cell tolerance in PDA which may underscore its resistance to immunotherapy.
|State||Published - Dec 1 2019|
Bibliographical noteFunding Information:
Cell sorting/flow cytometry technologies were provided by NYU Langone’s Cytometry and Cell Sorting Laboratory, which is supported in part by grant P30CA016087 from the National Institutes of Health/National Cancer Institute. The results published here are in part based upon data generated by the TCGA Research Network: https://www.cancer. gov/tcga.
© 2019, The Author(s).
ASJC Scopus subject areas
- Physics and Astronomy (all)
- Chemistry (all)
- Biochemistry, Genetics and Molecular Biology (all)