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See detailNatural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer.
Langers, Inge ULg; Renoux, Virginie; Reschner, Anca et al

in European journal of immunology (in press)

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 ... [more ▼]

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. This activation was bi-directional. Indeed, in the presence of HPV-VLPs, DCs further activated NK cells by inducing the upregulation of cell surface activation markers (CD69 and HLA-DR). The function of NK cells was also improved as shown by an increase in IFN-gamma secretion and cytotoxic activity against an HPV+ cell line. This crosstalk between NK cells and DCs needed CD40 interaction and IL-12p70 secretion, whereas NKG2D was not implicated. Our results provide insight into how VLPs interact with innate immune cells and how NK cells and DCs play a role in the immune response induced by this vaccine agent. This article is protected by copyright. All rights reserved. [less ▲]

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See detailOrigin and immunoescape of uterine cervical cancer
Van hede, Dorien ULg; Langers, Inge ULg; DELVENNE, Philippe ULg et al

in Presse Médicale (2014)

Human papillomavirus associated uterine cervical cancer is an important public health problem since it is classified as the fourth most common cancer in women worldwide with more than 500 000 recorded ... [more ▼]

Human papillomavirus associated uterine cervical cancer is an important public health problem since it is classified as the fourth most common cancer in women worldwide with more than 500 000 recorded cases. This review is focused on where and why HPV infection induces cervical cancers and how this virus avoids the host immune response. Immunological therapeutic approaches are also addressed. [less ▲]

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

Poster (2013, May)

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 preneoplastic 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-a and IFN-g) 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 detailRole of Gamma Delta T cells in HPV-induced Cancer Progression
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Poster (2013, January 28)

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See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, December 10)

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See detailRole of γδ T cells in HPV-induced cancer progression
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Poster (2012, December 10)

Detailed reference viewed: 24 (5 ULg)
See detailRole of γδ T cells in the tumoural progression of HPV-associated lesions
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Conference (2012, November 09)

Detailed reference viewed: 16 (1 ULg)
See detailHuman papillomavirus capsids trigger crosstalk between dendritic and NK cells
Langers, Inge ULg; Renoux, Virginie; Pirotte, Evelyne et al

Poster (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 ▲]

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See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, June 22)

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See detailRole of γδ T cells in HPV-induced cancer progression
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Poster (2012, June 22)

Detailed reference viewed: 20 (6 ULg)
See detailγδ T cells could promote cancer progression of HPV-induced lesions
Van hede, Dorien ULg; Bastin, Renaud; Francis, Floriane et al

Conference (2012, June 02)

Detailed reference viewed: 25 (5 ULg)
See detailOncogenic human papillomavirus could directly interact with Natural Killer cells
Renoux, Virginie; Bastin, Renaud ULg; Boniver, Jacques ULg et al

Poster (2012, May 04)

Detailed reference viewed: 10 (4 ULg)
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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)

Detailed reference viewed: 86 (35 ULg)
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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 ▲]

Detailed reference viewed: 114 (43 ULg)