References of "Renoux, Virginie"
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See detailNatural Killer cells - role in local tumor growth and metastasis
Langers, Inge ULg; Renoux, Virginie ULg; Thiry, Marc ULg et al

in Biologics: Targets and Therapy (2012)

Historically, the name of Natural Killer (NK) cells came from their natural ability to kill tumor cells in vitro. From the seventies to date, accumulating data highlighted the importance of NK cells in ... [more ▼]

Historically, the name of Natural Killer (NK) cells came from their natural ability to kill tumor cells in vitro. From the seventies to date, accumulating data highlighted the importance of NK cells in host immune response against cancer and in therapy-induced anti-tumor response. The recognition and the lysis of tumor cells by NK cells are regulated by a complex balance of inhibitory and activating signals. This review summarizes NK cell mechanisms to kill cancer cells, their role in host immune responses against tumor growth or metastasis and their implications in anti-tumor immunotherapies via cytokines, antibodies or in combination with other therapies. The regulatory role of NK cells in autoimmunity is also discussed. [less ▲]

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See detailγδ T cells could promote cancer progression of HPV-induced lesions
Van hede, Dorien ULg; Bastin, Renaud ULg; Francis, Floriane et al

Conference (2012, February 04)

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See detailProinflammatory Cytokines Induce Bronchial Hyperplasia and Squamous Metaplasia in Smokers: Implications for chronic obstructive pulmonary disease therapy.
Herfs, Michael ULg; Hubert, Pascale ULg; POIRRIER, Anne-Lise ULg et al

in American Journal of Respiratory Cell and Molecular Biology (2012), 47(1), 67-79

Tracheobronchial squamous metaplasia is common in smokers and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Whereas this ... [more ▼]

Tracheobronchial squamous metaplasia is common in smokers and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Whereas this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia is still unclear. In the present study, we investigated the implication of cigarette smoke-mediated pro-inflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. By using immunohistological techniques, we showed a higher epithelial expression of TNFalpha, IL-1beta and IL-6 as well as an activation of NF-kappaB and AP-1/MAPK signalling pathways in the respiratory tract of smoking patients compared to the normal ciliated epithelium of non-smoking patients. In addition, we demonstrated that these signalling pathways strongly influence the proliferation and the differentiation state of in vitro generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks and demonstrated that anti-TNFalpha (etanercept), anti-IL-1beta (anakinra) and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and squamous metaplasia development. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, administration of pro-inflammatory cytokine antagonists may have clinical application in the management of COPD patients. [less ▲]

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See detailHuman papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.
Renoux, Virginie ULg; Bisig, Bettina ULg; Langers, Inge ULg et al

in European journal of immunology (2011), 41(11), 3240-3252

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK cell infiltration in HPV-associated pre-neoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-alpha and IFN-gamma) in the presence of HPV-VLPs. Using flow cytometry and microscopy we observed that NK cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

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See detailImplication des cellules Natural Killer (NK) dans le développement des lésions associées à l'infection par les papillomavirus humains (HPV)
Renoux, Virginie ULg

Doctoral thesis (2011)

Persistent infections with high-risk papillomavirus (HPV) are associated with more than 25% of cancers induced by infectious agents. Nevertheless, the two vaccines preventing HPV infection have no ... [more ▼]

Persistent infections with high-risk papillomavirus (HPV) are associated with more than 25% of cancers induced by infectious agents. Nevertheless, the two vaccines preventing HPV infection have no therapeutic efficacy and it has been estimated that there will be no measurable decline of HPV-associated tumours before 2040. The immune system is able to control, at least partially, HPV infection and subsequent tumour development. Around 90% of HPV-infected women will clear the virus within two years, but the immune effectors responsible for this viral clearance are unknown. Hence, the aim of this study was to determine if Natural Killer (NK) cells could play a role in the immune response against HPV infection and related cancers. The first part of this work was focused on the in vitro interaction of NK cells with L1 and L1L2 Virus Like Particles (VLP) of HPV16. We observed that, in the presence of HPV-VLP, NK cells displayed a higher cytotoxic activity against HPV+ cells by increasing the exocytosis of their cytotoxic granules and by secreting TNF-α and IFN-γ. NK cell activation was correlated with a fast entry of HPV-VLP by macropinocytosis and we determined that cell surface CD16 expression was necessary for HPV internalization, but also for degranulation and cytokine production. In the second part, to understand the molecular mechanisms of HPV-VLP stimulation, we investigated the signalling pathways operating in NK cells to trigger their cytotoxic activity in the presence of viral particles. We observed that the MAP kinases ERK and p38 were phosphorylated in the presence of both L1 and L1L2 HPV-VLP. Using specific inhibitors, we demonstrated that phosphorylation of these MAPK was required for degranulation and cytokine secretion by NK cells in the presence of VLP. In conclusion, NK cell activity could be an important player in the immune response contributing to viral clearance and to regression of HPV-induced cervical lesions. [less ▲]

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See detailHPV triggers NK cell cytotoxic activity and cytokine secretion
Jacobs, Nathalie ULg; Renoux, Virginie ULg; Bisig, Bettina ULg et al

Conference (2011)

Background The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumor development as demonstrated by a higher tumor prevalence in immunodeficient patients ... [more ▼]

Background The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumor development as demonstrated by a higher tumor prevalence in immunodeficient patients. Around 90% of HPV-infected women will clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has been performed evaluating the direct interaction between HPV and Natural Killer (NK) cells although these cells play a key role in host resistance to virus and tumor. Methods/Results By immunochemistry, we demonstrated an NK cell infiltration in HPV+ squamous pre-neoplasic lesions. Since HPV cannot grow in vitro, virus-like particles (VLP) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed a higher cytotoxic activity (CD107 and chromium release assays) and cytokine production (TNF-α and IFN-γ) in the presence of HPV-VLP. Uptake of HPV-VLP by dendritic cells (DC) has been shown to induce their activation, therefore, we investigated by flow cytometry and microscopy whether the stimulation of NK cell activity is linked to VLP internalization. We observed a faster entry into these cells compared to DC. Furthermore, virus uptake by NK cells is mediated by macropinocytosis, whereas this entry is dependent on clathrin or caveolin endocytosis pathways in DC. Using NK cell lines expressing or not CD16 and blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, but also for degranulation and cytokine production. Conclusion Thus, we show for the first time that NK cells interact with HPV and could participate in the immune response against HPV-induced tumors. [less ▲]

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See detailVaccine against human papillomavirus (HPV)-associated lesions induces collaboration between natural killer and dendritic cells in vitro.
Langers, Inge ULg; Reschner, Anca ULg; Renoux, Virginie ULg et al

Poster (2010, December)

Cervical cancer, the second most frequent gynaecological malignancy in the world, is caused by infection with high-risk human papillomaviruses (HPV). HPV16 and/or 18 are detected in more than 70% of these ... [more ▼]

Cervical cancer, the second most frequent gynaecological malignancy in the world, is caused by infection with high-risk human papillomaviruses (HPV). HPV16 and/or 18 are detected in more than 70% of these tumours. Prophylactic HPV-L1 virus like particle (VLP) vaccines are highly efficient to protect against HPV16 and HPV18 infection, but not against established infection. In this context, we study the effect of HPV-VLP on natural killer cells (NK) and on the crosstalk between NK and Dendritic Cells (DC). In order to know if HPV-VLP are able to enter in NK cells, we used fluorescent HPV-VLP with flow cytometry and confocal microscopy. HPV-VLP were internalised more rapidly in NK cells than in DC. They were already detected inside NK cells after 10 min of contact at 37°C. We also observed in CD107 assays, that HPV-VLP induce degranulation of NK cytotoxic granules. Previous works have shown that HPV-VLP were able to activate DC. We confirmed these results and observed an increase of CD69 cell surface expression and IFN-γ production by NK cells in the presence of DC activated by VLP. Interestingly, NK cells seemed to further activate DC in the presence of VLP as shown by an up-regulation of HLA-DR and CD86 on DC. Moreover, NK cells in the presence of HPV-VLP induced the production of IL12p70, but not the immunosuppressive cytokine IL10. Our results suggest that NK cells could play a role in the activation of DC induced by HPV-VLP during the vaccination against cervical cancer. Supported by the Belgian FNRS-Télévie [less ▲]

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See detailCross talk between dendritic and natural killer cells in the presence of vaccine agent against cervical cancer
Langers, Inge ULg; Renoux, Virginie ULg; Reschner, Anca ULg et al

in Belgian Journal of Medical Oncology [=BJMO] (2010, January 30), 4

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See detailMechanisms of cell entry by human papillomaviruses: an overview.
Horvath, Caroline Aj; Boulet, Gaelle Av; Renoux, Virginie ULg et al

in Virology Journal (2010), 7

ABSTRACT: As the primary etiological agents of cervical cancer, human papillomaviruses (HPVs) must deliver their genetic material into the nucleus of the target cell. The viral capsid has evolved to ... [more ▼]

ABSTRACT: As the primary etiological agents of cervical cancer, human papillomaviruses (HPVs) must deliver their genetic material into the nucleus of the target cell. The viral capsid has evolved to fulfil various roles that are critical to establish viral infection. The particle interacts with the cell surface via interaction of the major capsid protein, L1, with heparan sulfate proteoglycans. Moreover, accumulating evidence suggests the involvement of a secondary receptor and a possible role for the minor capsid protein, L2, in cell surface interactions.The entry of HPV in vitro is initiated by binding to a cell surface receptor in contrast to the in vivo situation where the basement membrane has recently been identified as the primary site of virus binding. Binding of HPV triggers conformational changes, which affect both capsid proteins L1 and L2, and such changes are a prerequisite for interaction with the elusive uptake receptor. Most HPV types that have been examined, appear to enter the cell via a clathrin-dependent endocytic mechanism, although many data are inconclusive and inconsistent. Furthermore, the productive entry of HPV is a process that occurs slowly and asynchronously and it is characterised by an unusually extended residence on the cell surface.Despite the significant advances and the emergence of a general picture of the infectious HPV entry pathway, many details remain to be clarified. The impressive technological progress in HPV virion analysis achieved over the past decade, in addition to the improvements in general methodologies for studying viral infections, provide reasons to be optimistic about further advancement of this field.This mini review is intended to provide a concise overview of the literature in HPV virion/host cell interactions and the consequences for endocytosis. [less ▲]

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See detailLocal applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions.
Hubert, Pascale ULg; Doyen, Jean ULg; Capelle, Xavier ULg et al

in American Journal of Reproductive Immunology (2010), 64(2), 126-136

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished ... [more ▼]

Abstract Problem Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study To test if a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL). We performed two clinical trials with11 healthy women and 15 patients with LSIL. Results GM-CSF applications were well tolerated in all enrolled women and no difference in toxicity between the treated and placebo groups was observed during the follow up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increased APC and cytotoxic T lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-γ whereas no cellular immune response was observed before the treatment. Moreover, the anti-VLP antibody titers also increased after the treatment. Conclusion These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [less ▲]

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See detailHuman Papillomavirus Virus-Like particles and NK cell interactions:role of CD16
Renoux, Virginie ULg; Langers Inge; Clémenceau Béatrice et al

in International Immunology (2010), 22(suppl Pt 5), 17

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See detailRegulation of the Immune Response by Innate Lymphocyte and Dendritic Cell Cross Talk
Reschner, Anca ULg; Langers, Inge ULg; Renoux, Virginie ULg et al

in Welles, Lorraine (Ed.) Dendritic Cells: Types, Life Cycles and Biological Functions (2010)

Dendritic cell (DC) is the generic name of different professional antigen presenting cell sub-populations, which are responsible for the initiation of specific immune responses. Recently, DC have been ... [more ▼]

Dendritic cell (DC) is the generic name of different professional antigen presenting cell sub-populations, which are responsible for the initiation of specific immune responses. Recently, DC have been involved in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NKT or γδ T (T cells expressing γδ T cell receptor). The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that the cross-talk between innate lymphocytes and DC was found to be multi-directional, involving not only cell-cell contacts but also soluble factors which lead to lymphocyte activation and DC maturation. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumor cells and infectious agents. Interestingly, DC, NK and γδ T cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NKT cells have the ability to kill DC. This chapter will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses. [less ▲]

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See detailTCRγδ cells in HPV-associated cervical cancer
Renoux, Virginie ULg; de Leval, Laurence ULg; Waroux, Olivier ULg et al

in Acta Clinica Belgica (2008), 63

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See detailInteraction between virus like particles (VLP) and natural killer (NK) cells
Renoux, Virginie ULg; Dortu, Estelle ULg; Provenzano, Fabian et al

in Acta Clinica Belgica (2008), 2

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