Certain types of head and neck tumors use the MARCHF8 protein to survive in the body. It destroys MHCI molecules—key markers that the immune system uses to recognize infected or cancerous cells. This conclusion was reached by scientists from the Henry Ford Health Center. The study results were published in the journal Proceedings of the National Academy of Sciences (PNAS).

The findings concern forms of head and neck cancer associated with the human papillomavirus (HPV). Under normal conditions, cells signal abnormalities to the immune system using MHCI molecules, which present protein fragments on the cell surface. These “alarm signals” allow immune cells to identify and eliminate dangerous cells.

However, researchers found that the virus triggers the production of the MARCHF8 protein. This protein destroys MHCI molecules before they can reach the cell surface. As a result, the immune system simply does not “see” the tumor.

When scientists experimentally disabled the MARCHF8 gene, the situation changed dramatically. Immune cells began to actively infiltrate the tumor and destroy it. In particular, the activity of CD8+ T cells and natural killer cells—key components of anti-tumor defense—significantly increased.

Moreover, suppressing MARCHF8 improved the responsiveness of tumors that previously reacted poorly to immunotherapy. According to the researchers, combining the blockade of this mechanism with standard treatments could turn so-called “cold” tumors, which are barely recognized by the immune system, into “hot” ones that trigger a strong immune response.