γδ T cells could promote cancer progression of HPV-induced lesions via pro-angiogenic mechanisms

Abstract

High-risk human papillomavirus infection is the etiological agent of cervical cancer, the third cause of cancer-associated death in women worldwide. Gamma delta T cells (γδ T cells) represent a small population of T cells expressing a T cell receptor (TCR) composed of gamma and delta chains. Their role in the context of HPV-induced lesions was not investigated yet, but we previously showed an infiltration of γδ T cells in this cancer, suggesting a relationship between HPV-induced lesions and γδ T cells. The goal of this project is to study the role of γδ T cells in the immune response against HPV-induced tumours. In order to study the role of γδ T cells in HPV-induced lesions, we have established a mouse model by crossing transgenic mice expressing HPV16 oncogenic genes, which develop spontaneous skin lesions, with γδ T cell-deficient mice. Surprisingly, depletion of γδ T cells significantly delays development of HPVinduced lesions. In parallel, we observed by immunohistochemistry an increase of leukocyte infiltration in HPV-induced lesions in absence of γδ T cells. Then, we evaluated by flow cytometry the proportions of immune cell populations present in the mouse skin and we found a larger proportion of CD4+ T cells in HPV and HPV γδ T cell-deficient mice compared to normal mice. Since γδ T cells could induce angiogenesis when infiltrating tumors, we measured blood vessels density in mice skin sections and we observed a significantly increase of blood vessels density in HPV mice compared to HPV γδ T cells-deficient mice. Our results suggest that γδ T cells could promote cancer progression in the context of HPV-induced lesions. We will further characterise these cells to understand in which cellular and molecular mechanisms they are involved.