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However, high\u2010risk <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>s modulate immune cells to create an immunosuppressive microenvironment, and induce these immune cells to produce interleukin 10 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010). This production of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010, in conjunction with <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> infection, contributes to the appearance of cervical neoplastic lesions. We sought to characterize the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010\u2010producing cellular phenotype, and investigate the influence of host and <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> factors upon the induction of an immunosuppressive microenvironment. Immunohistochemical analysis demonstrated an increase in <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010 production by keratinocytes, macrophages and Langerhans cells in high\u2010grade cervical lesions and cervical cancer. This increase was more pronounced in patients older than 30\u00a0years, and was also correlated with high viral load, and infection with a single <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> type, particularly high\u2010risk <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>s. Our results indicate the existence of a highly immunosuppressive microenvironment composed of different <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201010\u2010producing cellular phenotypes in cervical cancer samples, and samples classified as high\u2010grade cervical lesions (cervical intraepithelial neoplasia stages <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>). The immunosuppressive microenvironment that developed for these different cellular phenotypes favours viral persistence and neoplastic progression.<\/jats:p>","DOI":"10.1111\/imm.12487","type":"journal-article","created":{"date-parts":[[2015,6,9]],"date-time":"2015-06-09T16:15:47Z","timestamp":1433866547000},"page":"113-121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Local immunosuppression induced by high viral load of human papillomavirus: characterization of cellular phenotypes producing interleukin\u201010 in cervical neoplastic lesions"],"prefix":"10.1111","volume":"146","author":[{"given":"Thiago Theodoro Martins","family":"Prata","sequence":"first","affiliation":[{"name":"Postgraduate Programme of Infectious and Parasitic Diseases School of Medicine Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Mareti","family":"Bonin","sequence":"additional","affiliation":[{"name":"Centre for Biological and Health Sciences Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alda Maria Teixeira","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Centre for Biological and Health Sciences Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cacilda Tezelli Junqueira","family":"Padovani","sequence":"additional","affiliation":[{"name":"Centre for Biological and Health Sciences Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos Eurico dos Santos","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Centre for Biological and Health Sciences Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Machado","sequence":"additional","affiliation":[{"name":"Multicentre Postgraduate Programme in Biochemistry and Molecular Biology Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00eas Aparecida","family":"Tozetti","sequence":"additional","affiliation":[{"name":"School of Medicine Federal University of Mato Grosso do Sul Campo Grande Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/87.11.796"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.115"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/345285"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djg018"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/428779"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21193"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2004.12.008"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02859.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.5306\/wjco.v5.i4.753"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.9.4283-4296.2001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.33"},{"key":"e_1_2_8_15_1","first-page":"533","article-title":"Increased number of IL\u20102, IL\u20102 receptor and IL\u201010 positive cells in premalignant lesions of the cervix","volume":"49","author":"Mindiola R","year":"2008","journal-title":"Invest Clin"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/07357900802112693"},{"key":"e_1_2_8_17_1","first-page":"369","article-title":"IL\u201010 expression is regulated by HPV E2 protein in cervical cancer cells","volume":"4","author":"Berm\u00fadez\u2010Morales VH","year":"2011","journal-title":"Mol Med Rep"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2001.1820102.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(02)00009-1"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/170.5.1077"},{"key":"e_1_2_8_21_1","unstructured":"International Agency for Research on Cancer (IARC). 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