Latent viruses inspire a new kidney cancer therapy

Study Title: HIF regulates several translated endogenous retroviruses: Effects on cancer immunotherapy

Publication: Cell – February 28, 2025, 11:00 a.m.

Dana-Farber Cancer Institute Corresponding Authors: Derin B. Keskin, PhD, Catherine J. Wu, MD, William G. Kaelin Jr., Md

Summary:

DANA-Farber's researchers found that usually deceased viral genes that rest in human genome can be activated in the most common form of kidney cancer (clear cell kidney cell carcinoma) and trigger an immune response against cancer. The human genome contains a viral DNA that was integrated into the genome code a long time ago. Under certain circumstances, a subgroup of this viral genes can continue to be reactivated to produce viral proteins. This study showed that if the tumor -uppressor – VHL is inactivated by a mutation – a license plate for clear cell cell cancer cell cells – these viruses in our genome (referred to as endogenous retrovires) rather produce their proteins, and that this process is called a human protein that is rushed when VHL is crumbled. The team also found that the cancer cells disassemble 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 mice suggest that these flags can be detected by the immune cells referred to as T cells and stimulate an immune response against cancer.

Meaning:

There is indications that kidney cancer, in contrast to most other forms of cancer, is sometimes eradicated by the immune system. Just how is not well understood. This study suggests that the immune system can use an attack on cancer cells that can show fragments of endogenous retroviral proteins due to the presence of cancer mutations on their surface. Discovery indicates the potential to examine new ways to use endogenous retroviruses in developing new immunotherapies.

Financing:

The Us Department of Defense, The National Institute of Health, Howard Hughes Medical Institute, Breast Cancer Research Foundation, Louis Goodman and Alfred Gilman, The Yale Cancer Center, Swiss National Science Foundation, The Kohlberg Chair at Harvard Medical School, The Trust Family, Michael Brigham, Pan-Mass Challenge, Hinda and Arthur Marcus Fund, The Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute, The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Breast Cancer Research Foundation.