Researchers from the GIGA Cellular and Molecular Immunology Laboratory (led by Nathalie Jacobs) and ULB’s Pharmacotherapy and Pharmaceutical Pharmacy Department (led by David Vermijlen) have investigated unconventional T lymphocytes cells expressing a receptor composed of γ and δ chains, in the specific case of human papillomavirus-induced (HPV) cervical cancer.
Of all tumor-infiltrating leukocytes, T cells bearing γδ T cell receptors have been associated with the most favorable prognosis. However, we show here, in a mouse model of carcinogenesis induced by human papillomavirus (HPV)-oncoproteins, that γδ T cells promoted the development of HPV-induced lesions.
Indeed, HPV-oncoprotein expression induced an infiltration of γδ T cells producing IL-17A, a proangiogenic cytokine, and a decreased density of anti-tumor Vγ5+ γδ T subsets. Supporting the clinical relevance of our observations, IL-17A+ γδ T cells were detected in human cervical cancer, where HPV-oncoproteins are highly expressed, but not in less advanced cervical lesions.
These results support the notion that viral oncoproteins can induce a switch from antitumoral to pro-tumoral γδ T subsets in solid tumors.