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

Authors
  • Van Hede, Dorien1, 2, 3
  • Polese, Barbara4
  • Humblet, Chantal1
  • Wilharm, Anneke5
  • Renoux, Virginie1
  • Dortu, Estelle6
  • de Leval, Laurence7
  • Delvenne, Philippe6
  • Desmet, Christophe J1
  • Bureau, Fabrice1
  • Vermijlen, David8, 3
  • Jacobs, Nathalie9
  • 1 Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium. , (Belgium)
  • 2 Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), 1050 Bruxelles, Belgium. , (Belgium)
  • 3 Institute for Medical Immunology, ULB, 6041 Gosselies, Belgium. , (Belgium)
  • 4 Laboratory of Immunoendocrinology, GIGA Research, University of Liège, 4000 Liège, Belgium. , (Belgium)
  • 5 Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. , (Germany)
  • 6 Experimental Pathology, GIGA Research, University of Liège, 4000 Liège, Belgium. , (Belgium)
  • 7 Pathologie Clinique, Institut Universitaire de Pathologie, CH-1011 Lausanne, Switzerland. , (Switzerland)
  • 8 Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), 1050 Bruxelles, Belgium; [email protected] [email protected] , (Belgium)
  • 9 Laboratory of Cellular and Molecular Immunology, GIGA Research, University of Liège, 4000 Liège, Belgium; [email protected] [email protected] , (Belgium)
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Oct 24, 2017
Volume
114
Issue
43
Identifiers
DOI: 10.1073/pnas.1712883114
PMID: 29073102
Source
Medline
Keywords
License
Unknown

Abstract

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.

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