Dohun Pyeon, Professor at Michigan State University College of Human Medicine in the Department of Microbiology, Genetics, and Immunology, comments on new research published in PNAS uncovering how HPV-positive cancers hide from the immune system:
“For years, we’ve known that certain cancers associated with the Human Papillomavirus, or HPV, lack the markers cells use to signal their abnormalities, known as MHCI molecules. Without these molecular red flags, the immune system simply doesn’t see that there is a problem with the cell.
We’ve now demonstrated how HPV coopts a protein called MARCHF8 to dismantle those markers before the immune system can recognize the cancer cells. When MARCHF8 was removed in experimental models, the immune system immediately began clearing the tumors – even in cases where standard immunotherapy had previously failed. By combining this new genetic approach with standard immunotherapy drugs, we were able to turn ‘cold’ tumors that typically ignore treatment into ‘hot’ tumors where the immune system can prevail.
This suggests that in the future, we might be able to help patients who currently have no other options by simply stopping the cancer from shredding its red flags.”
Title: The membrane-associated ubiquitin ligase MARCHF8 degrades MHC-I in HPV-positive head and neck cancer for immune evasion
Authors: Mohamed I. Khalil, Jie Wang, Lexi Vu, Canchai Yang, Congcong Yin, Smriti Chadha, Harrison Nabors, Daniel Vocelle, Danielle G. May, Rachel J. Chrisopulos, Craig C. Welbon, Li Zhou, Kyle J. Roux, William C. Spanos, Matthew P. Bernard, Qing-Sheng Mi, Dohun Pyeon
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