Rôle des lymphocytes T TCR γδ dans la progression des lésions associées à l'infection par les papillomavirus humains

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.