title: The tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity.
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.
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Damya
authors.initials: D
authors.lastname: Laoui
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Jiri
authors.initials: J
authors.lastname: Keirsse
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Morias
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Van Overmeire
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Xenia
authors.initials: X
authors.lastname: Geeraerts
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Yvon
authors.initials: Y
authors.lastname: Elkrim
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Mate
authors.initials: M
authors.lastname: Kiss
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Bolli
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Qods
authors.initials: Q
authors.lastname: Lahmar
authors.affiliation: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Dorine
authors.initials: D
authors.lastname: Sichien
authors.affiliation: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, 3000 Leuven, Belgium.|Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, K.U. Leuven, 3000 Leuven, Belgium.
authors.forename: Jens
authors.initials: J
authors.lastname: Serneels
authors.affiliation: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: Epirus Biopharmaceuticals NL, 3584 CM Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.affiliation: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, 3000 Leuven, Belgium.|Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, K.U. Leuven, 3000 Leuven, Belgium.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazzone
authors.affiliation: Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
authors.affiliation: Laboratory of Myeloid Cell Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium.|Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008264:Macrophages / Q000276:immunology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*