Open AccessHPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV ‐positive tumour cells
Author(s) -
Van den Bergh Johan M. J.,
Guerti Khadija,
Willemen Yannick,
Lion Eva,
Cools Nathalie,
Goossens Herman,
Vorsters Alex,
Van Tendeloo Viggo F. I.,
Anguille Sébastien,
Van Damme Pierre,
Smits Evelien L. J. M.
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12284
Subject(s) - cytotoxic t cell , immunology , innate immune system , immune system , biology , interleukin 12 , adjuvant , immunity , cytokine , in vitro , biochemistry
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.