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

Damya Laoui (), Jiri Keirsse, Yannick Morias, Eva Van Overmeire, Xenia Geeraerts, Yvon Elkrim, Mate Kiss, Evangelia Bolli, Qods Lahmar, Dorine Sichien, Jens Serneels, Charlotte L. Scott, Louis Boon, Patrick De Baetselier, Massimiliano Mazzone, Martin Guilliams and Jo A. Van Ginderachter ()
Additional contact information
Damya Laoui: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Jiri Keirsse: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Yannick Morias: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Eva Van Overmeire: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Xenia Geeraerts: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Yvon Elkrim: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Mate Kiss: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Evangelia Bolli: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Qods Lahmar: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Dorine Sichien: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center
Jens Serneels: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center
Charlotte L. Scott: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center
Louis Boon: Epirus Biopharmaceuticals NL
Patrick De Baetselier: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center
Massimiliano Mazzone: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center
Martin Guilliams: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center
Jo A. Van Ginderachter: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13720

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