Hidden Viruses in Our DNA May Help Fight Kidney Cancer

Dana-Farber researchers have discovered that in clear cell renal cell carcinoma, the most common type of kidney cancer, dormant viral genes embedded in the human genome can become reactivated. Once activated, these genes produce viral proteins that can trigger the immune system to recognize and attack the cancer, the journal Cell reported.

These viral genes are remnants of ancient viral infections that became part of human DNA over evolutionary time. Although most remain inactive, some can be reawakened under specific conditions, leading to the production of viral-like proteins.

This study showed that when the tumor suppressor gene VHL is inactivated by a mutation – a hallmark of clear cell renal cell cancer cells – these viruses in our genome (called endogenous retroviruses) are more likely to produce their proteins and that this process is driven by a human protein called HIF2, which is overabundant when VHL is crippled.

The team also found that the cancer cells break these viral proteins into fragments and present them on the cell surface as flags that have the potential to stimulate an immune response. Additional tests in human samples and in mice suggest that these flags can be detected by the immune cells called T cells and do stimulate an immune response against the cancer.

Evidence suggests that kidney cancer, unlike most other forms of cancer, is sometimes eradicated by the immune system. Exactly how is not well understood. This study suggests that the immune system can mount an attack on cancer cells that, due to the presence of cancer-driving mutations, present fragments of endogenous retroviral proteins on their surface.

The discovery points to the potential for investigating new ways to leverage endogenous retroviruses in the development of novel immunotherapies.

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