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human papillomavirus and NK cells

Shanhong Lu, Fernando Concha-Benavente, Gulidanna Shayan, Raghvendra M Srivastava, Sandra P Gibson, Lin Wang, William E Gooding, Robert L Ferris
OBJECTIVES: The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab...
March 2018: Oral Oncology
S Wagner, H Böckmann, S Gattenlöhner, J P Klussmann, C Wittekindt
Based on clinical and experimental data, oropharyngeal squamous cell carcinomas (OPSCC) associated with human papillomavirus (HPV) have been recognized as a distinct entity of head and neck cancers. However, outside of clinical trials, HPV status currently has no impact on treatment. The natural replication cycle of HPV takes place in epithelial cells, and is thus spatially separated from cytotoxic immune cells in the epidermis. Dendritic cells (Langerhans cells, LC), however, are frequent in this upper dermal layer...
April 2018: HNO
Lada A Koneva, Yanxiao Zhang, Shama Virani, Pelle B Hall, Jonathan B McHugh, Douglas B Chepeha, Gregory T Wolf, Thomas E Carey, Laura S Rozek, Maureen A Sartor
The incidence of human papillomavirus (HPV)-related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV+ HNSCC patients...
January 2018: Molecular Cancer Research: MCR
Steven F Gameiro, Ali Zhang, Farhad Ghasemi, John W Barrett, Anthony C Nichols, Joe S Mymryk
Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain...
September 10, 2017: Viruses
Andrew Yang, Shiwen Peng, Emily Farmer, Qi Zeng, Max A Cheng, Xiaowu Pang, T-C Wu, Chien-Fu Hung
BACKGROUND: Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer, the fourth leading cause of cancer death in females worldwide. We have previously shown that coadministration of DNA encoding L1 capsid protein of Bovine papillomavirus (BPV) can enhance the antigen-specific immune response elicited by a therapeutic HPV16-E7 DNA vaccination. In this study, we sought to generate and evaluate the immunogenicity of a therapeutic HPV16-E7 DNA vaccine that encodes the fusion construct of HPV16-E7 and BPV-L1...
2017: Cell & Bioscience
John Kc Chan
A significant fraction of nasopharyngeal and sinonasal tumors are associated with Epstein-Barr virus (EBV) or human papillomavirus (HPV). Nasopharyngeal carcinoma (NPC) and extranodal NK/T-cell lymphoma harbor EBV in practically all cases, although a small proportion of cases of the former harbor HPV. Sinonasal inverted papillomas harbor HPV in about 25% of cases. Sinonasal squamous cell carcinomas harbor transcriptionally active HPV in about 20% of cases, and limited data suggest that this subset has a better prognosis than the HPV-negative subset...
January 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
J Luis Espinoza, Viet H Nguyen, Hiroshi Ichimura, Trang T T Pham, Cuong H Nguyen, Thuc V Pham, Mahmoud I Elbadry, Katsuji Yoshioka, Junji Tanaka, Ly Q Trung, Akiyoshi Takami, Shinji Nakao
Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174...
December 20, 2016: Scientific Reports
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...
May 3, 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
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