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Nat Commun. 2016 Dec 23;7:13720. doi: 10.1038/ncomms13720.

The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity.

Author information

1
Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.
2
Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
3
Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.
4
Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
5
Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, 3000 Leuven, Belgium.
6
Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, K.U. Leuven, 3000 Leuven, Belgium.
7
Epirus Biopharmaceuticals NL, 3584 CM Utrecht, The Netherlands.

Abstract

Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8+ T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vaccination strongly induces anti-tumour CTLs. Our data might prove important for therapeutic interventions targeted at specific TADC subsets or their precursors.

PMID:
28008905
PMCID:
PMC5196231
DOI:
10.1038/ncomms13720
[Indexed for MEDLINE]
Free PMC Article

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