HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV‐positive tumour cells
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...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2014-07, Vol.18 (7), p.1372-1380 |
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| creator | 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. |
| description | 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. |
| doi_str_mv | 10.1111/jcmm.12284 |
| format | Article |
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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.</creator><creatorcontrib>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.</creatorcontrib><description>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.</description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.12284</identifier><identifier>PMID: 24979331</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Antigens ; Cell activation ; Cells, Cultured ; Cervical cancer ; Cervix ; Cytokines ; Cytotoxicity ; Dendritic cells ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dendritic Cells - pathology ; Female ; Human papillomavirus ; human papillomavirus vaccine ; Humans ; Immune system ; Immunity, Innate - immunology ; Immunophenotyping ; Inflammation ; Innate immunity ; Interleukin-15 - immunology ; Interleukin-15 - metabolism ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Killer Cells, Natural - pathology ; Lymphocytes - immunology ; Lymphocytes - metabolism ; Lymphocytes - pathology ; Mode of action ; Natural killer cells ; Original ; Papillomaviridae - immunology ; Papillomavirus Infections - immunology ; Papillomavirus Infections - pathology ; Papillomavirus Infections - prevention & control ; Papillomavirus Vaccines - therapeutic use ; Studies ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; T-Lymphocytes, Cytotoxic - pathology ; Toll-like receptors ; Tumors ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - pathology ; Uterine Cervical Neoplasms - prevention & control ; Vaccines ; virus‐like particles</subject><ispartof>Journal of cellular and molecular medicine, 2014-07, Vol.18 (7), p.1372-1380</ispartof><rights>2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.</rights><rights>2014. This work is published under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5184-71771ae5e5f60e935dc03e98ea37c2639633c102a6f12220b5c04c3d9dcd3d263</citedby><cites>FETCH-LOGICAL-c5184-71771ae5e5f60e935dc03e98ea37c2639633c102a6f12220b5c04c3d9dcd3d263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124021/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124021/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24979331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van den Bergh, Johan M. J.</creatorcontrib><creatorcontrib>Guerti, Khadija</creatorcontrib><creatorcontrib>Willemen, Yannick</creatorcontrib><creatorcontrib>Lion, Eva</creatorcontrib><creatorcontrib>Cools, Nathalie</creatorcontrib><creatorcontrib>Goossens, Herman</creatorcontrib><creatorcontrib>Vorsters, Alex</creatorcontrib><creatorcontrib>Van Tendeloo, Viggo F. I.</creatorcontrib><creatorcontrib>Anguille, Sébastien</creatorcontrib><creatorcontrib>Van Damme, Pierre</creatorcontrib><creatorcontrib>Smits, Evelien L. J. M.</creatorcontrib><title>HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV‐positive tumour cells</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description>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.</description><subject>Antigens</subject><subject>Cell activation</subject><subject>Cells, Cultured</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - pathology</subject><subject>Female</subject><subject>Human papillomavirus</subject><subject>human papillomavirus vaccine</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunity, Innate - immunology</subject><subject>Immunophenotyping</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>Interleukin-15 - immunology</subject><subject>Interleukin-15 - metabolism</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Killer Cells, Natural - pathology</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes - metabolism</subject><subject>Lymphocytes - pathology</subject><subject>Mode of action</subject><subject>Natural killer cells</subject><subject>Original</subject><subject>Papillomaviridae - immunology</subject><subject>Papillomavirus Infections - immunology</subject><subject>Papillomavirus Infections - pathology</subject><subject>Papillomavirus Infections - prevention & control</subject><subject>Papillomavirus Vaccines - therapeutic use</subject><subject>Studies</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - pathology</subject><subject>Toll-like receptors</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - immunology</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Uterine Cervical Neoplasms - prevention & control</subject><subject>Vaccines</subject><subject>virus‐like particles</subject><issn>1582-1838</issn><issn>1582-4934</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kcFuFSEYhYnR2Frd-ACGxI1pcis_DDPDxsTcWKtpowt1Syj8U7nOwHVgrt5dH8Fn9EnkeqeNupANJP_H4RwOIY-BnUBZz1d2GE6A87a6Qw5BtnxRKVHdnc_QivaAPEhpxZioQaj75IBXqlFCwCG5Pnv_iW6MtT4gTdkPU28yJmq3Oeb43VtqbPYbn7c0dvSL73scqcPgRp_L0GLfJ2qCo8HkaTT9DTIProwPKdPyyM_rH-uYyqUN0jwNcZqZh-ReZ_qEj-b9iHw8ffVhebY4f_f6zfLl-cJKaKtFA00DBiXKrmaohHSWCVQtGtFYXgtVC2GBcVN35Sc4u5SWVVY45awTrgBH5MVedz1dDugshlzs6vXoBzNudTRe_z0J_rO-ihtdAa8YhyLwbBYY49cJU9aDT7sIJmCckgYpGWtaqFVBn_6DrkreUOLp0pKSdau4LNTxnrJjTGnE7tYMML0rVu-K1b-LLfCTP-3fojdNFgD2wDff4_Y_Uvrt8uJiL_oLX6qxdA</recordid><startdate>201407</startdate><enddate>201407</enddate><creator>Van den Bergh, Johan M. 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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. 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J.</au><au>Guerti, Khadija</au><au>Willemen, Yannick</au><au>Lion, Eva</au><au>Cools, Nathalie</au><au>Goossens, Herman</au><au>Vorsters, Alex</au><au>Van Tendeloo, Viggo F. I.</au><au>Anguille, Sébastien</au><au>Van Damme, Pierre</au><au>Smits, Evelien L. J. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV‐positive tumour cells</atitle><jtitle>Journal of cellular and molecular medicine</jtitle><addtitle>J Cell Mol Med</addtitle><date>2014-07</date><risdate>2014</risdate><volume>18</volume><issue>7</issue><spage>1372</spage><epage>1380</epage><pages>1372-1380</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><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. 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| source | Open Access: DOAJ - Directory of Open Access Journals; Wiley-Blackwell Journals; MEDLINE; Wiley Open Access; PubMed Central; EZB Electronic Journals Library |
| subjects | Antigens Cell activation Cells, Cultured Cervical cancer Cervix Cytokines Cytotoxicity Dendritic cells Dendritic Cells - immunology Dendritic Cells - metabolism Dendritic Cells - pathology Female Human papillomavirus human papillomavirus vaccine Humans Immune system Immunity, Innate - immunology Immunophenotyping Inflammation Innate immunity Interleukin-15 - immunology Interleukin-15 - metabolism Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Killer Cells, Natural - pathology Lymphocytes - immunology Lymphocytes - metabolism Lymphocytes - pathology Mode of action Natural killer cells Original Papillomaviridae - immunology Papillomavirus Infections - immunology Papillomavirus Infections - pathology Papillomavirus Infections - prevention & control Papillomavirus Vaccines - therapeutic use Studies T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism T-Lymphocytes, Cytotoxic - pathology Toll-like receptors Tumors Uterine Cervical Neoplasms - immunology Uterine Cervical Neoplasms - pathology Uterine Cervical Neoplasms - prevention & control Vaccines virus‐like particles |
| title | HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV‐positive tumour cells |
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