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

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 th...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-10, Vol.114 (43), p.E9056
Main Authors: Van hede, Dorien, Polese, Barbara, Humblet, Chantal, Wilharm, Anneke, Renoux, Virginie, Dortu, Estelle, de Leval, Laurence, Delvenne, Philippe, Desmet, Christophe J, Bureau, Fabrice, Vermijlen, David, Jacobs, Nathalie
Format: Article
Language:English
Subjects:
Angiogenesis
Animal models
Blood vessels
Cancer
Carcinogenesis
Carcinogens
CCR6 protein
Cervix
Cytokines
Dermis
Human papillomavirus
Lesions
Leukocytes
Lymphocytes
Lymphocytes T
Oncoproteins
Skin
Squamous cell carcinoma
Subpopulations
Transgenic mice
Uterine cancer
Uterus
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Summary: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+ γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6+ γδlowCCR2+CCR6-) 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+ 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.
ISSN:0027-8424
1091-6490