Immune Response to Commensal Viruses Protects Mice from Skin Cancer

Infection with certain human papillomaviruses (HPV) has been associated with squamous cell carcinomas, particularly among immunocompromised people, but the reason for the proposed link is unclear. In contrast, Strickley, Messerschmidt, and colleagues found that T cell–based adaptive immunity to commensal papillomaviruses may be protective against skin cancer, and that the loss of such immunity—rather than direct oncogenic effects of viral infection—may be responsible for the increased skin-cancer risk seen in immunocompromised people. Infecting mice with mouse papillomavirus type 1 (MmuPV1) led to a delay in the development of skin tumors caused by exposure to chemical carcinogens. Importantly, mice who had acquired immunity to MmuPV1 via T-cell transfer from MmuPV1-exposed mice were also protected against the cancer-promoting effects of chemical carcinogens applied to the skin or exposure to ultraviolet radiation. Demonstrating the potential implications of these findings in humans, there was substantially lower β-HPV activity and load in human skin cancer compared with adjacent normal tissue. This implies that there may be immune selection against β-HPV–positive cancer cells, a notion supported by the fact that E7 peptides from β-HPVs led to CD8⁺ T-cell activation in healthy human skin. This study is notable because it reveals that immunity against certain commensal viruses is worth investigating further in skin cancer, and especially whether boosting immunity to such viruses may be a worthwhile strategy. Additionally, this work adds to the growing body of research on the roles of the human skin virome.

Strickley JD, Messerschmidt JL, Awad ME, Li T, Hasegawa T, Ha DT, et al. Immunity to commensal papillomaviruses protects against skin cancer. Nature 2019 Oct 30 [Epub ahead of print].

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