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T-cell Immunity Against Papillomaviruses Protects Against Skin Cancer

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Originally published on Nature

Key findings

  • ß–human papillomavirus (ß-HPV) has been considered a potential cause of cutaneous squamous cell carcinoma (SCC)
  • In contradiction to this theory, Massachusetts General Hospital researchers and colleagues observed suppression of skin cancer in immunocompetent mice infected with papillomavirus
  • When tested for 25 known commensal HPVs (those that are low-risk and commonly resident on the skin), human SCC samples showed significantly reduced viral load and viral activity compared with adjacent healthy tissue
  • Healthy human skin exhibited CD8+ T cells specific for ß-HPV, indicative of resident adaptive immunity to the virus in the skin
  • T cell–based vaccines against commensal HPVs may boost adaptive immunity and prove to be a novel approach to preventing skin cancer

Immunosuppressed individuals are at more than 100-fold greater risk of cutaneous squamous cell carcinoma (SCC) than the general population. In turn, more than 80% of SCCs in immunosuppressed organ transplant recipients contain β–human papillomavirus (β-HPV).

Therefore, β-HPV has been considered a potential cause of SCC, even though no β-HPV types are predominant in patients with skin cancer. Researchers have conjectured that β-HPV facilitates initiation of skin cancer in the presence of a weakened immune system and is later lost during tumor maintenance.

Shawn Demehri, MD, PhD, of the Center for Cancer Research at Massachusetts General Hospital, and colleagues have turned this "hit-and-run" theory on its head. They found preclinical evidence that T-cell immunity against papillomaviruses suppresses skin cancer in immunocompetent hosts. As they explain in Nature, loss of this immunity in immunocompromised people may be what increases their risk of SCC.

Mouse Models

Still intending to investigate how papillomaviruses drive skin cancer, the researchers infected several strains of immunocompetent mice with mouse papillomavirus. To their surprise, after long-term exposure to carcinogenic chemicals, those mice exhibited significant delay in skin tumor onset compared with sham-infected mice and had significantly lower tumor burden. In one strain of mice, some individuals demonstrated complete immunity or antiviral adaptive immunity.

Results were similar when mice were exposed to ultraviolet light. Furthermore, transfer of memory T cells from immune mice into non-immune mice also resulted in protection against skin carcinogenesis.

Human Tissue

The researchers then tested human SCC samples for 25 known commensal β-HPVs (those that are low-risk and commonly resident on the skin). Compared with adjacent normal skin, cancer tissue showed significantly reduced viral load and viral activity in both immunocompetent and immunosuppressed patients.

Moreover, in healthy human skin the team discovered CD8+ T cells specific for β-HPV, indicative of adaptive immunity. T cell–based vaccines against commensal HPVs may boost adaptive immunity and prove to be a novel approach to preventing skin cancer.

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