Article (Scientific journals)
Human papillomavirus oncoproteins induce a reorganization of epithelial-associated gammadelta T cells promoting tumor formation.
Van hede, Dorien; Polese, Barbara; Humblet, Chantal et al.
2017In Proceedings of the National Academy of Sciences of the United States of America, 114 (43), p. 9056-E9065
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Keywords :
functional heterogeneity; gammadelta; interleukin 17; viral oncogene; gammadelta T cells
Abstract :
[en] 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.
Research center :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
GIGA‐R - Giga‐Research - ULiège
d‐BRU - Dental Biomaterials Research Unit - ULiège [BE]
Disciplines :
Oncology
Microbiology
Immunology & infectious disease
Author, co-author :
Van hede, Dorien ;  Université de Liège - ULiège
Polese, Barbara ;  Université de Liège - ULiège > R&D Direction : Chercheurs ULiège en mobilité
Humblet, Chantal ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Histologie - Cytologie
Wilharm, Anneke
Renoux, Virginie
Dortu, Estelle
de Leval, Laurence
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Desmet, Christophe  ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Bureau, Fabrice ;  Université de Liège - ULiège > Département des sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Vermijlen, David
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Virologie
Language :
English
Title :
Human papillomavirus oncoproteins induce a reorganization of epithelial-associated gammadelta T cells promoting tumor formation.
Publication date :
2017
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Volume :
114
Issue :
43
Pages :
E9056-E9065
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Fonds Léon Fredericq [BE]
Commentary :
Published under the PNAS license.
Available on ORBi :
since 27 October 2017

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