References of "Jacobs, Nathalie"
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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)

Detailed reference viewed: 48 (12 ULg)
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See detailNovel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue
EL SHAZLY, Amr ULg; Castillo-Doloriert, Hugo; Bisig, Bettina et al

Poster (2013)

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed ... [more ▼]

Background: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/ CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy.
Objective: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. Methods: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. Results: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. Conclusions and Clinical Relevance: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]

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See detailExpansion of CD16+ CD56+ NK cells in vericyte® NK cell growth medium
Brohée, Laura ULg; Bastin, Renaud ULg; Wingert, S et al

Poster (2013)

Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation ... [more ▼]

Natural Killer (NK) cells play a key role in host resistance to virus and tumour. These cells are potent killers of virus infected and tumour cells via a direct recognition of the target by activation receptor such as NKG2D or by inducing Fcγ receptor (FcγRIII, CD16) mediated antibody dependent cellular cytotoxicity (ADCC). Current NK cell-based cancer immunotherapy aims to produce large amounts of functional NK cells, unfortunately most culture media used for NK cell expansion induced the downregulation of CD16 on NK cells. Here, we tested the impact of a new NK cell growth medium (Vericyte® from Medicyte) on CD16 expression. Sorted NK cells and peripheral blood mononuclear cells (PBMC) were cultivated in vericyte® NK cell growth medium and cells issued from these cultures were characterized in term of expansion and phenotype at several time points. After 5 days of culture, an expansion of both NK cells and PBMC was observed and maintained at least until day 20 of culture. In PBMC cultures, we observe only a small preferential NK cell growth since NK cells were around 5-10% at beginning of the culture and this percentage increased to 15% at the end of the culture. However, these cells showed a high proliferative potential when we started the culture with sorted NK cells (the proportion of contaminant cells remain low, under 5%). NK cells expressed CD56 and NKp46 and interestingly after a decreased expression of CD16 on the cell surface at day 3, this receptor was up regulated and most of the cells are CD56bright CD16bright from day 7 to day 12. According FACS FCS/SSC dot plot, NK cells acquired morphology of large activated lymphocytes and some of them expressed activation markers such CD25. Finally, these cells were able to kill efficiently tumour cell line K562. Thus our data show that vericyte® NK cell growth medium allows the expansion of functional CD16+CD56+ NK cells. Cytokine production and ADCC function are under investigation. [less ▲]

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See detailNovel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue.
EL SHAZLY, Amr ULg; Castillo- Doloriert, Hugo; Bisig, Bettina et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (2013), 43(3), 322-31

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed ... [more ▼]

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. OBJECTIVE: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. METHODS: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. RESULTS: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. CONCLUSIONS AND CLINICAL RELEVANCE: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway. [less ▲]

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See detailInterleukin-32 expression is associated with a poorer prognosis in head and neck squamous cell carcinoma.
Guenin, Samuel; Mouallif, Mustapha ULg; Hubert, Pascale ULg et al

in Molecular Carcinogenesis (2013)

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes ... [more ▼]

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes carcinogenesis as well as the formation of metastasis. Indeed, proinflammatory mediators are known to stimulate the expression of specific transcription factors such as Snai1 and to increase the ability of tumor cells to migrate into distant organs. The atypical interleukin-32 (IL32) was mainly described to exacerbate inflammatory responses in rheumatoid arthritis and inflammatory bowel diseases. IL32 is expressed in various cancers but its role in HNSCC physiology is still unexplored. Here, we analyzed the expression of IL32 and its implication on HNSCC aggressiveness. We showed that patients with tumor expressing high amounts of IL32 exhibit decreased disease-free periods (20.5 mo vs. 41 mo, P = 0.0041) and overall survival (P = 0.0359) in comparison with individuals with weak IL32 tumor expression. This overexpression was negatively correlated with gender (P = 0.0292) and p53 expression (P = 0.0307). In addition, in vitro data linked IL32 expression to metastasis formation since IL32 inhibition decreased Snai1 expression and tumor cell migration in a Boyden chamber assay. Our data provide new insight into the role of IL32 in HNSCC aggressiveness. (c) 2013 Wiley Periodicals, Inc. [less ▲]

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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: 22 (4 ULg)
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)

Detailed reference viewed: 20 (13 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: 15 (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 ▲]

Detailed reference viewed: 23 (6 ULg)
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)

Detailed reference viewed: 5 (2 ULg)
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: 18 (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: 23 (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 ▲]

Detailed reference viewed: 73 (22 ULg)