Journal of Clinical Investigation Publishes New Cancer Research by Lead Author Yu Leo Lei
February 24, 2020
Ann Arbor, Mich. - A research team led by School of Dentistry faculty member Yu Leo Lei has published a new study advancing the understanding of how tumors suppress the innate immune system.
Yu Leo Lei
Published today in the Journal of Clinical Investigation, the study, “HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING,” utilized multiple methodologies to derive new insights into head and neck tumor development associated with human papillomavirus (HPV). The incidence of HPV-positive Head and Neck Squamous Cell Carcinoma (HNSCC) has surpassed that of HPV-positive cervical cancers and is predicted to continue to grow for decades into the future, even after adjustment for the use of HPV vaccines among women.
Despite the expression of viral proteins, which should be recognized by human immune system, these tumors are still largely invisible to immune cells. This is in part evidenced by their lower-than-anticipated response rates to cancer immunotherapies. Before a tumor-specific adaptive immune response can develop, the innate immune system serves as the first line of defense against initiating tumors. However, how tumors escape from innate immune surveillance remains unknown.
“This study found a striking and potent mechanism that HPV utilizes to shut down the innate immune system and avoid being targeted by the immune cells,” said Lei. “HPV16, which is an HPV subtype that drives over 90 percent of the HPV-positive HNSCC, encodes a protein, E7, to induce tumor cell proliferation. We found a previously unknown function of HPV16 E7 in promoting the degradation of a central molecule that activates the innate type-I interferon response."
Additionally, the study characterized the molecular mechanisms that drive HPV16-induced innate immune tolerance. Overall, the study represents a conceptual advance in the understanding of how tumors suppress the innate immune system.
Lei is Assistant Professor of Dentistry in the Department of Periodontics and Oral Medicine and adjunct Assistant Professor of Otolaryngology – Head and Neck Surgery at Michigan Medicine. The Lei Lab focuses on translational immunology research.
