title: Ag-presenting CpG-activated pDCs prime Th17 cells that induce tumor regression.
abstract: Plasmacytoid dendritic cells (pDC) rapidly and massively produce type I IFN and other inflammatory cytokines in response to foreign nucleic acids, thereby indirectly influencing T-cell responses. Moreover, antigen (Ag)-presenting pDCs directly regulate T-cell differentiation. Depending on the immune environment, pDCs exhibit either tolerogenic or immunogenic properties. Here, we show that CpG-activated pDCs promote efficient Th17 differentiation. Indeed, Th17 responses are defective in mice selectively lacking MHCII on pDCs upon antigenic challenge. Importantly, in those mice, the frequency of Th17 cells infiltrating solid tumors is impaired. As a result, the recruitment of infiltrating leukocytes in tumors, including tumor-specific cytotoxic T lymphocytes (CTL), is altered and results in increased tumor growth. Importantly, following immunization with tumor Ag and CpG-B, MHCII-restricted Ag presentation by pDCs promotes the differentiation of antitumor Th17 cells that induce intratumor CTL recruitment and subsequent regression of established tumors. Our results highlight a new role for Ag presenting activated pDCs in promoting the development of Th17 cells and impacting on antitumor immunity.
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Leslie
authors.initials: L
authors.lastname: Guéry
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Dubrot
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Carla
authors.initials: C
authors.lastname: Lippens
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Dale
authors.initials: D
authors.lastname: Brighouse
authors.affiliation: NovImmune SA, Geneva, Switzerland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Malinge
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. Centre d'immunology de Marseille Luminy, Université de la Méditerranée, Marseille, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Irla
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Pot
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Waldburger
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. Stephanie.hugues@unige.ch.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hugues
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000502:physiology*; D015226:Dinucleoside Phosphates / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015226:Dinucleoside Phosphates; D000949:Histocompatibility Antigens Class II; C015772:CpG dinucleotide