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Doctoral thesis (Dissertations and theses)
Rôle des lymphocytes T TCR γδ dans la progression des lésions associées à l'infection par les papillomavirus humains
Van Hede, Dorien
2017
 

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Keywords :
HPV; cancer du col de l'utérus; lymphocytes T γδ
Abstract :
[en] 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.
Research center :
d‐BRU - Dental Biomaterials Research Unit - ULiège [BE]
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Biochemistry, biophysics & molecular biology
Immunology & infectious disease
Reproductive medicine (gynecology, andrology, obstetrics)
Author, co-author :
Van Hede, Dorien ;  Centre Hospitalier Universitaire de Liège - CHU > Service de médecine dentaire
Language :
French
Title :
Rôle des lymphocytes T TCR γδ dans la progression des lésions associées à l'infection par les papillomavirus humains
Defense date :
27 June 2017
Institution :
ULiège - Université de Liège
Degree :
Doctorat en Sciences biomédicales et pharmaceutiques
Promotor :
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Vermijlen, David
President :
Cataldo, Didier  ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Secretary :
Gillet, Laurent  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Jury member :
Desmet, Christophe  ;  Université de Liège - ULiège > GIGA > GIGA I3 - Cellular and Molecular Immunology
Gilles, Christine ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Goriely, Stanislas
Déchanet-Merville, Julie
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Fonds Léon Fredericq [BE]
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since 26 June 2017

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