Potential Melanoma Treatment Breakthrough: Is KDM5B the Key?

The enzyme KDM5B may suppress anti-melanoma immunity, and this could help lead to the development of a new treatment strategy to benefit patients with melanoma and other cancers.

The enzyme KDM5B may suppress anti-melanoma immunity, and these findings could help lead to the development of a new treatment strategy to benefit patients with melanoma and other cancers, according to a new study out of  the Yale Cancer Center in New Haven, Conn.

The research is published online in the journal Nature.

“These results are exciting as we discovered fundamental roles of some poorly studied genetic elements in immune responses and identified a new way to stimulate the ability of our immune system to fight cancer,” says Dr. Qin Yan, associate professor of pathology and director of the Epigenetics Program in the Department of Pathology and a member of Yale Cancer Center, in a news release. “In addition, we showed that this method can be used to overcome the resistance to current cancer immunotherapies.”

In the study, researchers show depletion of the protein KDM5B, which is critical for melanoma maintenance and drug resistance, induces robust adaptive immune responses, and enhances responses to immune checkpoint blockade. KDM5B partners with SETDB1, a protein-coding gene, to repress the expression of certain genetic elements such as MMVL30. Expression of these genetic elements stimulates RNA and DNA sensing pathways and subsequent interferon responses, leading to tumor rejection and immune memory.

Yan and his team have been studying the roles of KDM5 proteins cancer for many years. This work began when researchers began examining the roles of KDM5B in melanoma in close collaboration with the lab of fellow Yale researcher Dr. Marcus Bosenberg, a co-corresponding author of the new study. Resources and expertise provided by the Yale Center for Immuno-Oncology and the Yale SPORE in Skin Cancer were critical for this research.

“It is urgent to find new strategies to render immunotherapies effective to help treat patients with cancer,” says Bosenberg.

Adds Yan: “We’re encouraged as now we’re working on dissecting how these genetic elements contribute to cancer and developing specific cancer drugs based on our discovery.”