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See detailRôle des lymphocytes T TCR γδ dans la progression des lésions associées à l'infection par les papillomavirus humains
Van Hede, Dorien ULiege

Doctoral thesis (2017)

Cervical cancer was the fourth most frequent cancer in women in 2012, with the majority of cases occurring in less developed countries. Although this cancer is induced by Human Papillomavirus (HPV ... [more ▼]

Cervical cancer was the fourth most frequent cancer in women in 2012, with the majority of cases occurring in less developed countries. Although this cancer is induced by Human Papillomavirus (HPV) infections that have a high prevalence, only a very few percentage of infected women will developed this disease. Host immune defenses are essential to clear infection and to kill virus-infected transformed cells. Indeed, majority of infected women clear the virus within two years while immunocompromised patients are more likely to develop cervical preneoplastic lesions and cancers. γδ T cells have been shown to protect against the formation of squamous cell carcinoma (SCC) in several models. Nowadays, the contribution of γδ T cells in HPV associated uterine cervical SCC is unknown. Here we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16-oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16-oncoprotein-induced lesions. These oncoproteins induced a decrease in epidermal Skint-1 expression and modification of the associated anti-tumor Vγ5+ γδ T cells (or DETC), which were joined by other γδ T cell subsets actively producing IL-17. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical, IL-17+ γδ T cells could be only observed at the cancer stage (SCC) (but not in less advanced cervical lesions), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16-oncoproteins induce a reorganization of the local epithelial-associated γδ T cell Subpopulations thereby promoting angiogenesis and cancer development. [less ▲]

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See detailHuman papillomavirus oncoproteins induce a reorganization of epithelial-associated gammadelta T cells promoting tumor formation.
Van hede, Dorien ULiege; Polese, Barbara ULiege; Humblet, Chantal ULiege et al

in Proceedings of the National Academy of Sciences of the United States of America (2017), 114(43), 9056-9065

It has been shown that gammadelta T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of gammadelta T cells in human papillomavirus (HPV)-associated ... [more ▼]

It has been shown that gammadelta T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of gammadelta T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of gammadelta T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, gammadelta T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vgamma5+ gammadelta T cells, which were replaced by gammadelta T-cell subsets (mainly Vgamma6+ gammadeltalowCCR2+CCR6-) actively producing IL-17A. Consistent with a proangiogenic role, gammadelta T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A+ gammadelta T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated gammadelta T-cell subpopulations, thereby promoting angiogenesis and cancer development. [less ▲]

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See detailOrigin and immunoescape of uterine cervical cancer
Van hede, Dorien ULiege; Langers, Inge ULiege; DELVENNE, Philippe ULiege 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 detailRole of Gamma Delta T cells in HPV-induced Cancer Progression
Van hede, Dorien ULiege; Bastin, Renaud; Francis, Floriane et al

Poster (2013, January 28)

Detailed reference viewed: 82 (17 ULiège)
See detailRole of γδ T cells in HPV-induced cancer progression
Van hede, Dorien ULiege; Bastin, Renaud; Francis, Floriane et al

Poster (2012, December 10)

Detailed reference viewed: 38 (9 ULiège)
See detailRole of γδ T cells in the tumoural progression of HPV-associated lesions
Van hede, Dorien ULiege; Bastin, Renaud; Francis, Floriane et al

Conference (2012, November 09)

Detailed reference viewed: 26 (7 ULiège)
See detailRole of γδ T cells in HPV-induced cancer progression
Van hede, Dorien ULiege; Bastin, Renaud; Francis, Floriane et al

Poster (2012, June 22)

Detailed reference viewed: 38 (11 ULiège)
See detailγδ T cells could promote cancer progression of HPV-induced lesions
Van hede, Dorien ULiege; Bastin, Renaud; Francis, Floriane et al

Conference (2012, June 02)

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

Conference (2012, February 04)

Detailed reference viewed: 101 (38 ULiège)