title: Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner.
abstract: The contribution of natural killer (NK) cells to the treatment efficacy of dendritic cell (DC)-based cancer vaccines is being increasingly recognized. Much current efforts to optimize this form of immunotherapy are therefore geared towards harnessing the NK cell-stimulatory ability of DCs. In this study, we investigated whether generation of human monocyte-derived DCs with interleukin (IL)-15 followed by activation with a Toll-like receptor stimulus endows these DCs, commonly referred to as "IL-15 DCs", with the capacity to stimulate NK cells. In a head-to-head comparison with "IL-4 DCs" used routinely for clinical studies, IL-15 DCs were found to induce a more activated, cytotoxic effector phenotype in NK cells, in particular in the CD56bright NK cell subset. With the exception of GM-CSF, no significant enhancement of cytokine/chemokine secretion was observed following co-culture of NK cells with IL-15 DCs. IL-15 DCs, but not IL-4 DCs, promoted NK cell tumoricidal activity towards both NK-sensitive and NK-resistant targets. This effect was found to require cell-to-cell contact and to be mediated by DC surface-bound IL-15. This study shows that DCs can express a membrane-bound form of IL-15 through which they enhance NK cell cytotoxic function. The observed lack of membrane-bound IL-15 on "gold-standard" IL-4 DCs and their consequent inability to effectively promote NK cell cytotoxicity may have important implications for the future design of DC-based cancer vaccine studies.
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Anguille
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Van Acker
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van den Bergh
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Willemen
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Viggo F
authors.initials: VF
authors.lastname: Van Tendeloo
authors.affiliation: Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium; Center for Oncological Research, University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Evelien L
authors.initials: EL
authors.lastname: Smits
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Zwi N
authors.initials: ZN
authors.lastname: Berneman
authors.affiliation: Laboratory of Experimental Hematology, Tumor Immunology Group (TIGR), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Lion
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D019409:Interleukin-15 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation
chemical_list: D019002:CD56 Antigen; D016207:Cytokines; C569274:IL15 protein, human; D019409:Interleukin-15; C522918:NCAM1 protein, human