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人乳头瘤病毒疫苗可刺激杀伤性树突状细胞和自然杀伤细胞对人乳头瘤病毒阳性肿瘤细胞的细胞毒性活性。

HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells.

作者信息

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

机构信息

Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium.

出版信息

J Cell Mol Med. 2014 Jul;18(7):1372-80. doi: 10.1111/jcmm.12284. Epub 2014 Jun 30.

DOI:10.1111/jcmm.12284
PMID:24979331
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4124021/
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.

摘要

希瑞适™被批准作为一种预防性疫苗，用于预防与宫颈癌发生有因果关系的人乳头瘤病毒（HPV）16型和18型感染。我们首次在体外研究了这种HPV疫苗对白细胞介素（IL）-15树突状细胞（DC）（作为血液DC天然存在亚群的替代物）以及自然杀伤（NK）细胞（两种在抗肿瘤免疫中起重要作用的先天免疫细胞类型）的影响。我们的结果表明，IL-15 DC暴露于HPV疫苗会导致表型成熟标志物表达增加、促炎细胞因子产生以及对HPV阳性肿瘤细胞的细胞毒性活性增强。这些效应由疫苗佐剂介导，部分通过Toll样受体4激活。接下来，我们证明暴露于疫苗的IL-15 DC反过来会诱导NK细胞的表型激活，从而对HPV感染的肿瘤细胞产生协同细胞毒性作用。因此，我们的研究确定了HPV疫苗在增强先天免疫方面的一种新作用模式，包括DC和NK细胞对HPV感染细胞的杀伤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/83dc60f41ddc/jcmm0018-1372-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/3ba174c2326e/jcmm0018-1372-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/9b96955436f7/jcmm0018-1372-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/d016bc7dd1ba/jcmm0018-1372-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/83dc60f41ddc/jcmm0018-1372-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/3ba174c2326e/jcmm0018-1372-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/9b96955436f7/jcmm0018-1372-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/d016bc7dd1ba/jcmm0018-1372-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f0e/4124021/83dc60f41ddc/jcmm0018-1372-f4.jpg

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