title: HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells.
abstract: Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells.
authors: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Johan M J
authors: JM
authors: Van den Bergh
authors: Khadija
authors: K
authors: Guerti
authors: Yannick
authors: Y
authors: Willemen
authors: Eva
authors: E
authors: Lion
authors: Nathalie
authors: N
authors: Cools
authors: Herman
authors: H
authors: Goossens
authors: Alex
authors: A
authors: Vorsters
authors: Viggo F I
authors: VF
authors: Van Tendeloo
authors: Sébastien
authors: S
authors: Anguille
authors: Pierre
authors: P
authors: Van Damme
authors: Evelien L J M
authors: EL
authors: Smits
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control
chemical_list: D019409:Interleukin-15; D053918:Papillomavirus Vaccines
keywords: cytotoxicity; dendritic cells; human papillomavirus vaccine; natural killer cells; virus-like particles