title: Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells.
abstract: Dendritic cells (DCs) cross-present antigen (Ag) to initiate T-cell immunity against most infections and tumors. Natural killer (NK) cells are innate cytolytic lymphocytes that have emerged as key modulators of multiple DC functions. Here, we show that human NK cells promote cross-presentation of tumor cell-derived Ag by DC leading to Ag-specific CD8(+) T-cell activation. Surprisingly, cytotoxic function of NK cells was not required. Instead, we highlight a critical and nonredundant role for IFN-γ and TNF-α production by NK cells to enhance cross-presentation by DC using two different Ag models. Importantly, we observed that NK cells promote cell-associated Ag cross-presentation selectively by monocytes-derived DC (Mo-DC) and CD34-derived CD11b(neg) CD141(high) DC subsets but not by myeloid CD11b(+) DC. Moreover, we demonstrate that triggering NK cell activation by monoclonal antibodies (mAbs)-coated tumor cells leads to efficient DC cross-presentation, supporting the concept that NK cells can contribute to therapeutic mAbs efficiency by inducing downstream adaptive immunity. Taken together, our findings point toward a novel role of human NK cells bridging innate and adaptive immunity through selective induction of cell-associated Ag cross-presentation by CD141(high) DC, a process that could be exploited to better harness Ag-specific cellular immunity in immunotherapy.
authors.affiliation: Inserm UMR-S1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France; UNIV UMR1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Université de Lyon, Lyon, France; Centre Léon Bérard, Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Deauvieau
authors.forename: Vincent
authors.initials: V
authors.lastname: Ollion
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Doffin
authors.forename: Carole
authors.initials: C
authors.lastname: Achard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fonteneau
authors.forename: Estelle
authors.initials: E
authors.lastname: Verronese
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durand
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ghittoni
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Marvel
authors.forename: Colette
authors.initials: C
authors.lastname: Dezutter-Dambuyant
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.forename: Henri
authors.initials: H
authors.lastname: Vie
authors.forename: Ivan
authors.initials: I
authors.lastname: Perrot
authors.forename: Nadège
authors.initials: N
authors.lastname: Goutagny
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Jenny
authors.initials: J
authors.lastname: Valladeau-Guilemond
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm
keywords: NK cell; cross-presentation; dendritic cell; mAb therapy