Specialized dendritic cells induce tumor-promoting IL-10<sup>+</sup>IL-17<sup>+</sup> FoxP3<sup>neg</sup> regulatory CD4<sup>+</sup> T cells in pancreatic carcinoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30926808.
- Also identified by DOI 10.1038/s41467-019-09416-2 and PMC identifier 6441038.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The drivers and the specification of CD4<sup>+</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<sub>H</sub>-program. Specifically, CD11b<sup>+</sup>CD103<sup>-</sup> DC predominate in PDA, express high IL-23 and TGF-β, and induce FoxP3<sup>neg</sup> tumor-promoting IL-10<sup>+</sup>IL-17<sup>+</sup>IFNγ<sup>+ </sup>regulatory CD4<sup>+</sup> T cells. The balance between this distinctive T<sub>H</sub> program and canonical FoxP3<sup>+ </sup>T<sub>REGS</sub> is unaffected by pattern recognition receptor ligation and is modulated by DC expression of retinoic acid. This T<sub>H</sub>-signature is mimicked in human PDA where it is associated with immune-tolerance and diminished patient survival. Our data suggest that CD11b<sup>+</sup>CD103<sup>-</sup> DC promote CD4<sup>+</sup> T cell tolerance in PDA which may underscore its resistance to immunotherapy.
Medical subject headings
- Dendritic Cells
- Interleukin-10
- Interleukin-17
- Pancreatic Neoplasms
- T-Lymphocytes, Regulatory