A team of scientists at Henry Ford Health + Michigan State University Health Sciences have uncovered a mechanism that allows certain head and neck cancers to hide from the immune system, a discovery that could change how some of the most treatment resistant tumors are approached. The study, published in Proceedings of the National Academy of Sciences, identifies a single protein at the heart of this invisibility and shows that removing it can make hidden tumors vulnerable to treatment.
For years, physicians and researchers have known that these cancers, which are associated with the Human Papillomavirus, or HPV, lack the markers cells use to signal distress, known as MHCI molecules. Without these molecular red flags, the immune system simply doesn’t see that there is a problem with the cell. Until now, the field had only fragments of the explanation.
The team — led by Dohun Pyeon, professor in the Department of Microbiology, Genetics, & Immunology — has now demonstrated that HPV co-opts a protein called MARCHF8 to dismantle those markers before the immune system can recognize the cancer cells. When the researchers removed MARCHF8 in experimental models, the immune system immediately began clearing the tumors — even in cases where standard immunotherapy had previously failed.