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human papillomavirus and NK cells

Emmanouil Papasavvas, Lea F Surrey, Deborah K Glencross, Livio Azzoni, Jocelin Joseph, Tanvier Omar, Michael D Feldman, Anna-Lise Williamson, Maureen Siminya, Avril Swarts, Xiangfan Yin, Qin Liu, Cynthia Firnhaber, Luis J Montaner
Persistence of human papillomavirus (HPV) and cervical disease in the context of HIV co-infection can be influenced by introduction of antiretroviral therapy (ART) and sustained immune activation despite ART. We conducted a cross-sectional study in order to evaluate immune activation/exhaustion in ART-suppressed HIV(+) women with or without high-risk (HR) HPV-related cervical intraepithelial neoplasia (CIN). 55 South African women were recruited in three groups: HR (-) (n = 16) and HR (+) (n = 15) HPV with negative cervical histopathology, and HR (+) HPV with CIN grade 1/2/3 (n = 24)...
May 2016: Oncoimmunology
Louis Cicchini, Joseph A Westrich, Tao Xu, Daniel W Vermeer, Jennifer N Berger, Eric T Clambey, Denis Lee, John I Song, Paul F Lambert, Robert O Greer, John H Lee, Dohun Pyeon
UNLABELLED: High-risk human papillomaviruses (HPVs) are causally associated with multiple human cancers. Previous studies have shown that the HPV oncoprotein E7 induces immune suppression; however, the underlying mechanisms remain unknown. To understand the mechanisms by which HPV deregulates host immune responses in the tumor microenvironment, we analyzed gene expression changes of all known chemokines and their receptors using our global gene expression data sets from human HPV-positive and -negative head/neck cancer and cervical tissue specimens in different disease stages...
2016: MBio
Steffen Wagner, Claus Wittekindt, Miriam Reuschenbach, Ben Hennig, Mauran Thevarajah, Nora Würdemann, Elena-Sophie Prigge, Magnus von Knebel Doeberitz, Thomas Dreyer, Stefan Gattenlöhner, Jens Peter Klussmann
Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by bead-based hybridization (Luminex technology)...
May 1, 2016: International Journal of Cancer. Journal International du Cancer
Brunna M Alves, Isabel M Prellwitz, Juliana D Siqueira, Ângela R Meyrelles, Anke Bergmann, Héctor N Seuánez, Elizabeth S Machado, Marcelo A Soares, Esmeralda A Soares
Patients with compromised immune systems have more severe intraepithelial lesions and more rapid disease progression, in addition to increased risk for cervical cancer. Persistent infection by the human papillomavirus (HPV) is a necessary step in that process. By inducing expression of inhibitory ligands of natural killer cells, like HLA-G, HPV avoids the elimination of infected cells. Recent studies have investigated polymorphisms in HLA-G that may be associated with susceptibility to HPV infection and persistence...
August 2015: Infection, Genetics and Evolution
Alexandra V Lucs, James A DeVoti, Lynda Hatam, Ali Afzal, Allan L Abramson, Bettie M Steinberg, Vincent R Bonagura
Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway...
March 2015: Journal of Clinical Medicine
Iwona Hus, Joanna Gonet-Sebastianka, Agata Surdacka, Agnieszka Bojarska-Junak, Jacek Roliński
Persistent infection with oncogenic types of human papillomavirus (HPV) is a causal factor for more than 99% of cervical cancers. Recently, prophylactic vaccines have been developed to prevent infections with cancer-associated HPV types (HPV16 and HPV18). The aim of this study was to analyze the changes in the immune system that occur within four weeks of the first dose of HPV-16/18 ASO4-adjuvanted vaccine. Assessment of the percentages of selected cell populations in peripheral blood of 20 healthy volunteers vaccinated with Cervarix was performed using flow cytometry...
2015: Postȩpy Higieny i Medycyny Doświadczalnej
Ting Hu, Pei Yang, Hongmei Zhu, Xinlian Chen, Xiaoyan Xie, Mei Yang, Shanling Liu, He Wang
BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown. METHODS: In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled...
2015: Diagnostic Pathology
Changdong Li, Cui Ma, Weiyuan Zhang, Jiandong Wang
INVESTIGATION: To study the differences immune function in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical cancer tissue, and study the relationship between human papillomavirus (HPV) infection and cervical local immune function. MATERIALS AND METHODS: This study determined the form, quantity, distribution, and intensity of CD4+Th cells, S-100+ dendritic cells (DCs) and CD57+NK cells in the normal cervical tissue, CIN cervical tissue, and cervical cancer by histopathological and image analyses...
2014: European Journal of Gynaecological Oncology
Changdong Li, Cui Ma, Weiyuan Zhang, Jiandong Wang
INVESTIGATION: To study the differences immune function in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical cancer tissue, and study the relationship between human papillomavirus (HPV) infection and cervical local immune function. MATERIALS AND METHODS: This study determined the form, quantity, distribution, and intensity of CD4+Th cells, S-100+ dendritic cells (DCs) and CD57+NK cells in the normal cervical tissue, CIN cervical tissue, and cervical cancer by histopathological and image analyses...
2014: European Journal of Gynaecological Oncology
Tzu-Yu Liu, Ashwini Kumar Giddam, Waleed M Hussein, Zhongfan Jia, Nigel A J McMillan, Michael J Monteiro, Istvan Toth, Mariusz Skwarczynski
Vaccine candidates for the treatment of human papillomavirus (HPV)-associated cancers are aimed to activate T-cells and induce development of cytotoxic anti-tumor specific responses. Peptide epitopes derived from HPV-16 E7 oncogenic protein have been identified as promising antigens for vaccine development. However, peptide-based antigens alone elicit poor cytotoxic T lymphocyte (CTL) responses and need to be formulated with an adjuvant (immunostimulant) to achieve the desired immune responses. We have reported the ability of polyacrylate 4-arm star-polymer (S4) conjugated with HPV-16 E744-57 (8Qmin) epitope to reduce and eradicate TC-1 tumor in the mouse model...
2015: Current Drug Delivery
Inge Langers, Virginie Renoux, Anca Reschner, Antoine Touzé, Pierre Coursaget, Jacques Boniver, Joachim Koch, Philippe Delvenne, Nathalie Jacobs
Virus-like particles (VLPs) of human papillomavirus (HPV) are used as a vaccine against HPV-induced cancer, and recently we have shown that these VLPs are able to activate natural killer (NK) cells. Since NK cells collaborate with dendritic cells (DCs) to induce an immune response against viral infections and tumors, we studied the impact of this crosstalk in the context of HPV vaccination. NK cells in the presence of HPV-VLPs enhanced DC-maturation as shown by an upregulation of CD86 and HLA-DR and an increased production of IL-12p70, but not of the immunosuppressive cytokine IL-10...
December 2014: European Journal of Immunology
Edith M G van Esch, Mariette I E van Poelgeest, Simone Kouwenberg, E Michelle Osse, J Baptist M Z Trimbos, Gert Jan Fleuren, Ekaterina S Jordanova, Sjoerd H van der Burg
Human papillomavirus-induced usual-type vulvar intraepithelial neoplasia (uVIN) are infiltrated by immune cells but apparently not cleared. A potential explanation for this is an impaired T cell effector function by an immunesuppressive milieu, coinfiltrating regulatory T cells or the expression of coinhibitory molecules. Here, the role of these potential inhibitory mechanisms was evaluated by a detailed immunohistochemical analysis of T cell infiltration in the context of FoxP3, Tbet, indoleamine 2,3-dioxygenase, programmed cell death 1, T cell immunoglobulin mucin 3 (TIM3), natural killer cell lectin-like receptor A (NKG2A) and galectins-1, -3 and -9...
February 15, 2015: International Journal of Cancer. Journal International du Cancer
Pascale Hubert, Ludivine Herman, Patrick Roncarati, Catherine Maillard, Virginie Renoux, Stéphanie Demoulin, Charlotte Erpicum, Jean-Michel Foidart, Jacques Boniver, Agnès Noël, Philippe Delvenne, Michael Herfs
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses...
December 2014: Journal of Pathology
Roberta Rizzo, Valentina Gentili, Antonella Rotola, Daria Bortolotti, Enzo Cassai, Dario Di Luca
Human papillomavirus (HPV) regulation of host immune response leads to cervical lesions. In particular, natural killer (NK) cells are crucial for HPV control. Since specific HLA-I/KIR interactions modify NK cell activation, we analyzed HLA-C and KIR alleles in HPV infection and lesion development in 150 controls, 33 condyloma acuminatum, and 111 invasive cervical cancer (ICC) patients. We showed an increase in HLA-C1/KIR2DL2 and HLA-C1/KIR2DL3 pairs in HPV high-risk infected patients (OR 3.05, 3.24) with ICC (OR 1...
November 2014: Viral Immunology
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
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...
July 2014: Journal of Cellular and Molecular Medicine
Jie Zhao, Wanjiang Zeng, Yuchun Cao, Xiaoyu Liang, Bo Huang
Condylomata acuminata (CA), caused by human papillomavirus (HPV), is a common sexually transmitted disease with half a million new cases diagnosed in the United States per year and an annual increase in incidence in China. Conventional treatments, including topical cytotoxic agents, surgical excision and physical therapies, are traumatic, cause local side-effects and are invalid for subclinical or latent infection. Exploring immune approaches to eradicate HPV in CA therapeutics are highly desirable. Recent evidence shows that FOXP3(+) regulatory T (Treg) cells are accumulated in genital warts where they mediate immunosuppression...
June 2014: Expert Review of Clinical Immunology
Nuchsupha Sunthamala, Chamsai Pientong, Tatsukuni Ohno, Chenyang Zhang, Arundhati Bhingare, Yuta Kondo, Miyuki Azuma, Tipaya Ekalaksananan
The balance between active immune responses against human papillomavirus (HPV) and HPV-induced immune escape regulates viral clearance and carcinogenesis. To understand the role of the early viral protein HPV16 E2 in host innate immune responses, the HPV16 E2-transfected murine squamous cell carcinoma cell line SCCVII (SCC/E2) was generated and anti-tumor responses in T-cell-depleted mice were evaluated. Tumor growth of SCC/E2 was markedly reduced. Cytotoxicity against the NK-sensitive targets YAC-1 and SCCVII was clearly enhanced in SCC/E2-inoculated mice...
April 18, 2014: Biochemical and Biophysical Research Communications
Alexis Régent, Brigitte Autran, Guislaine Carcelain, Rémi Cheynier, Benjamin Terrier, Bénédicte Charmeteau-De Muylder, Alain Krivitzky, Eric Oksenhendler, Nathalie Costedoat-Chalumeau, Pascale Hubert, Olivier Lortholary, Nicolas Dupin, Patrice Debré, Loïc Guillevin, Luc Mouthon
Idiopathic CD4 T lymphocytopenia (ICL) is a rare and severe condition with limited available data. We conducted a French multicenter study to analyze the clinical and immunologic characteristics of a cohort of patients with ICL according to the Centers for Disease Control criteria.We recruited 40 patients (24 female) of mean age 44.2 ± 12.2 (19-70) years. Patients underwent T-lymphocyte phenotyping and lymphoproliferation assay at diagnosis, and experiments related to thymic function and interferon (IFN)-γ release by natural killer (NK) cell were performed...
March 2014: Medicine (Baltimore)
Huimin Guo, Ruili Hu, Xinlei Guan, Fang Guo, Shuzhen Zhao, Xueying Zhang
The aim of the present study was to investigate the cytotoxicity of natural killer (NK) cells to CaSki cells following knockdown of the E7 protein of the human papillomavirus type 16 (HPV16E7). Recombinant adenovirus-short hairpin-E7 protein of the human panillomavirus type 16 (Ad‑sh‑HPV16E7) was constructed and used to infect CaSki cells. The expression of HPV16E7 in CaSki cells was assessed using western blot analysis. The expression of cell surface molecule major histocompatibility complex‑I (MHC‑I) in CaSki cells infected with Ad‑sh‑HPV16E7 was examined using flow cytometry...
April 2014: Molecular Medicine Reports
Alfred Bere, Shahila Tayib, Jean-Mari Kriek, Lindi Masson, Shameem Z Jaumdally, Shaun L Barnabas, William H Carr, Bruce Allan, Anna-Lise Williamson, Lynette Denny, Jo-Ann S Passmore
HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV+ women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+ women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p = 0...
February 2014: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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