HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV‐positive tumour cells |
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| Authors: | Johan M. J. Van den Bergh Khadija Guerti Yannick Willemen Eva Lion Nathalie Cools Herman Goossens Alex Vorsters Viggo F. I. Van Tendeloo Sébastien Anguille Pierre Van Damme Evelien L. J. M. Smits |
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| Affiliation: | 1. Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, , Antwerp, Belgium;2. Division of Immunology, Department of Laboratory Medicine, Antwerp University Hospital, , Edegem, Belgium;3. Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, , Antwerp, Belgium;4. Centre for the Evaluation of Vaccination (CEV), Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, , Antwerp, Belgium;5. Center for Oncological Research Antwerp, Faculty of Medicine & Health Sciences, University of Antwerp, , Antwerp, Belgium |
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| 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. |
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| Keywords: | human papillomavirus vaccine dendritic cells natural killer cells virus‐like particles cytotoxicity |
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