MSU Cracks Code: Revealing HPV-positive Cancer's Cloak

Discovery could lead to new cancer therapies for treatment-resistant tumors

Mar. 19, 2026 at 6:35am

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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. The study, published in Proceedings of the National Academy of Sciences, identifies a single protein called MARCHF8 that HPV uses to dismantle the molecular red flags cells use to signal distress to the immune system. 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.

Why it matters

HPV-positive head and neck cancer cases have increased at epidemic rates in the United States over the past few decades. The discovery opens a potential path to new cancer therapies, pointing to the development of drugs that block MARCHF8 to treat patients who currently have no effective treatment options.

The details

The team, led by Dohun Pyeon, Ph.D., professor in the Department of Microbiology, Genetics, & Immunology, has now demonstrated that HPV coopts 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. The effect was striking. Without MARCHF8, immune cells such as CD8+ T cells and natural killer cells rapidly entered the tumor microenvironment, restoring an immune response that had been absent.

  • The study was published in Proceedings of the National Academy of Sciences in 2026.

The players

Dohun Pyeon

Professor in the Department of Microbiology, Genetics, & Immunology at Michigan State University and the lead researcher on the study.

Mohamed Khalil

Research assistant professor in the Department of Microbiology, Genetics, & Immunology at Michigan State University and the first author on the paper.

Qing-Sheng Mi

Vice chair for research in the MSU Department of Dermatology, director of the Center for Cutaneous Biology and Immunology, and director of the immunology program of the Henry Ford Cancer Institute at Henry Ford Health. Mi is also professor of medicine at the MSU College of Human Medicine and served as the co-principal investigator on this project.

Henry Ford Health

A health system that collaborated with Michigan State University Health Sciences on this research.

Michigan State University Health Sciences

The university that led the research team that uncovered the mechanism allowing certain head and neck cancers to hide from the immune system.

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What they’re saying

“The most exciting part is that our discovery worked on tumors that were previously impossible to treat.”

— Dohun Pyeon, Professor, Department of Microbiology, Genetics, & Immunology, Michigan State University

“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.”

— Dohun Pyeon, Professor, Department of Microbiology, Genetics, & Immunology, Michigan State University

“We found that the MARCHF8 knockout activated T cells and enhanced T cells, natural killer cells, and macrophage infiltration into the tumor microenvironment. I think we have very promising hope for targeting MARCHF8.”

— Mohamed Khalil, Research Assistant Professor, Department of Microbiology, Genetics, & Immunology, Michigan State University

“We showed knocking out MARCHF8 fundamentally rewires immune cell crosstalk — dramatically boosting the cytotoxic activity of CD8+ T cells and NK cells. It revealed not just that the therapy works, but precisely how and why.”

— Qing-Sheng Mi, Vice Chair for Research, Department of Dermatology, Michigan State University; Director, Center for Cutaneous Biology and Immunology; Director, Immunology Program, Henry Ford Cancer Institute

What’s next

The researchers plan to determine how different immune cells assist T cells in killing tumor cells once the MHCI markers are restored. Their goal is to develop a drug that blocks MARCHF8 in humans, which would allow doctors to combine the new MARCHF8-blocking therapy with existing immunotherapies to offer a lifeline to patients with tumors that currently resist all other treatments.

The takeaway

This discovery opens a potential path to new cancer therapies for HPV-positive head and neck cancers, which have seen a dramatic increase in the U.S. in recent decades. By targeting the MARCHF8 protein that allows these cancers to hide from the immune system, researchers hope to develop a new treatment approach that can be combined with existing immunotherapies to help patients who currently have no effective options.