Role of Gamma Delta T cells in HPV-induced Cancer ProgressionVan hede, Dorien ; ; et alPoster (2013, January 28) Detailed reference viewed: 18 (3 ULg) Role of γδ T cells in HPV-induced cancer progressionVan hede, Dorien ; ; et alPoster (2012, December 10) Detailed reference viewed: 16 (4 ULg) Oncogenic human papillomavirus could directly interact with Natural Killer cells; Bastin, Renaud ; Boniver, Jacques et alPoster (2012, December 10) Detailed reference viewed: 11 (9 ULg) Role of γδ T cells in the tumoural progression of HPV-associated lesionsVan hede, Dorien ; ; et alConference (2012, November 09) Detailed reference viewed: 11 (1 ULg) Human papillomavirus capsids trigger crosstalk between dendritic and NK cellsLangers, Inge ; ; Pirotte, Zoé et alPoster (2012, September 26) The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumour development as demonstrated by a higher tumour prevalence in immunodeficient patients. More than ... [more ▼] The immune system controls, at least partially, human papillomavirus (HPV) infection and subsequent tumour development as demonstrated by a higher tumour prevalence in immunodeficient patients. More than 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 although dendritic cells (DC) and NK cells play a key role in host resistance to virus and tumour, no study has been performed evaluating their crosstalk in this context. Virus-like particles (VLP) formed by the HPV major capsid protein L1 are licensed as vaccine against cervical cancer and we have recently shown that NK cells can directly interact with these HPV-VLP [1]. Here, we investigated the impact of this activation on NK-DC crosstalk. Interestingly, NK cells increase DC maturation induced by HPV-VLP as shown by an up-regulation of HLA-DR and CD86 on DC. Transwell experiments indicated that the expression of HLA-DR is cell-cell contact and soluble factor dependent, whereas only soluble factors seem to be required for CD86 expression. Moreover, in the presence of HPV-VLP and NK cells, DC produce higher amounts of IL12p70, while the production of the immunosuppressive cytokine IL10 remains unchanged. We also demonstrated that DC can up-regulate the expression of NK activation markers (CD69 and HLA-DR) in the presence of HPV-VLP. This up-regulation requires both cell-cell contact and soluble factors. Regarding HLA-DR marker, the increased expression on CD56bright cells is mediated by soluble factors, whereas cell-cell contacts are also important for HLA-DR expression on CD56dim cells. In the presence of DC activated by HPV-VLP, the function of NK cells is also modified since they become more cytotoxic against HPV+ cell line and secrete more IFN-γ. Our results suggest that NK-DC crosstalk could play a role in the immune response induced by HPV-VLP during vaccination protocols against cervical cancer. [less ▲] Detailed reference viewed: 7 (3 ULg) The human papillomavirus (HPV) vaccine induces collaboration between dendritic cells and natural killer cells in vitroLangers, Inge ; ; Dortu, Estelle et alConference (2012, June 22) Detailed reference viewed: 15 (7 ULg) Oncogenic human papillomavirus could directly interact with Natural Killer cells; Bastin, Renaud ; Boniver, Jacques et alPoster (2012, June 22) Detailed reference viewed: 4 (2 ULg) Role of γδ T cells in HPV-induced cancer progressionVan hede, Dorien ; ; et alPoster (2012, June 22) Detailed reference viewed: 15 (6 ULg) γδ T cells could promote cancer progression of HPV-induced lesionsVan hede, Dorien ; ; et alConference (2012, June 02) Detailed reference viewed: 17 (4 ULg) The human papillomavirus vaccine induces collaboration between dendritic cells and natural killer cells in vitroLangers, Inge ; ; Dortu, Estelle et alPoster (2012, May 04) Detailed reference viewed: 9 (3 ULg) Oncogenic human papillomavirus could directly interact with Natural Killer cells; Bastin, Renaud ; Boniver, Jacques et alPoster (2012, May 04) Detailed reference viewed: 6 (4 ULg) Natural Killer cells - role in local tumor growth and metastasisLangers, Inge ; Renoux, Virginie ; Thiry, Marc et alin 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 ▲] Detailed reference viewed: 52 (19 ULg) Human papillomavirus entry triggers NK cell cytotoxic activity and cytokine secretionRenoux, Virginie ; Bastin, Renaud ; Langers, Inge et alPoster (2012, March 28) Detailed reference viewed: 76 (49 ULg) γδ T cells could promote cancer progression of HPV-induced lesionsVan hede, Dorien ; Bastin, Renaud ; et alConference (2012, February 04) Detailed reference viewed: 70 (32 ULg) Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.Renoux, Virginie ; Bisig, Bettina ; Langers, Inge et alin 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 ▲] Detailed reference viewed: 80 (39 ULg) Macropinocytosis of human papillomaviruses in natural killer cells via CD16 induces cytotoxic granule exocytosis and cytokine secretionRenoux, Virginie ; Langers, Inge ; et alPoster (2011, September 13) Detailed reference viewed: 20 (5 ULg) HPV triggers NK cell cytotoxic activity and cytokine secretionJacobs, Nathalie ; Renoux, Virginie ; Bisig, Bettina et alConference (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 ▲] Detailed reference viewed: 30 (5 ULg) Vaccine against human papillomavirus (HPV)-associated lesions induces collaboration between natural killer and dendritic cells in vitro.Langers, Inge ; Reschner, Anca ; Renoux, Virginie et alPoster (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 ▲] Detailed reference viewed: 38 (4 ULg) Cross talk between dendritic and natural killer cells in the presence of vaccine agent against cervical cancerLangers, Inge ; Renoux, Virginie ; Reschner, Anca et alin Belgian Journal of Medical Oncology [=BJMO] (2010, January 30), 4 Detailed reference viewed: 58 (24 ULg) Regulation of the Immune Response by Innate Lymphocyte and Dendritic Cell Cross TalkReschner, Anca ; Langers, Inge ; Renoux, Virginie et alin 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 ▲] Detailed reference viewed: 66 (26 ULg) |
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