Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.

Détails

Ressource 1Télécharger: PMID29073102.pdf (1630.47 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_7B747A7BC526
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Human papillomavirus oncoproteins induce a reorganization of epithelial-associated γδ T cells promoting tumor formation.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Van Hede D., Polese B., Humblet C., Wilharm A., Renoux V., Dortu E., de Leval L., Delvenne P., Desmet C.J., Bureau F., Vermijlen D., Jacobs N.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
24/10/2017
Peer-reviewed
Oui
Volume
114
Numéro
43
Pages
E9056-E9065
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ 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 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. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 <sup>+</sup> γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 <sup>+</sup> γδ <sup>low</sup> CCR2 <sup>+</sup> CCR6 <sup>-</sup> ) actively producing IL-17A. 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 biopsies, IL-17A <sup>+</sup> γδ 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 γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development.
Mots-clé
Animals, Cervix Uteri, Epidermis/pathology, Epidermis/virology, Female, Humans, Immunoglobulins/metabolism, Interleukin-17/metabolism, Intraepithelial Lymphocytes/pathology, Intraepithelial Lymphocytes/virology, Mice, Transgenic, Neoplasms, Squamous Cell/pathology, Neoplasms, Squamous Cell/virology, Neovascularization, Pathologic, Oncogene Proteins, Viral/metabolism, Papillomavirus E7 Proteins/metabolism, Papillomavirus Infections/pathology, Papillomavirus Infections/virology, Receptors, CCR2/metabolism, Receptors, CCR6/metabolism, Repressor Proteins/metabolism, Uterine Cervical Neoplasms/pathology, Uterine Cervical Neoplasms/virology, functional heterogeneity, gammadelta, interleukin 17, viral oncogene, γδ T cells
Pubmed
Web of science
Open Access
Oui
Création de la notice
31/10/2017 10:38
Dernière modification de la notice
08/05/2019 20:49
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