Researchers Discover How Melanoma Evades the Immune System

Researchers from Sanford Burnham have found that a protein known to be active in immune cells is also active inside melanoma cells, helping promote tumor growth, suggesting that targeting this protein with new drugs may deliver a powerful double hit to melanoma tumors.

Because immunotherapy is the first-line therapy for several cancers today, the researchers sought to find ways to boost immunotherapy in melanoma by analyzing data from patient tumors to identify genes that may coincide with patients’ responsiveness to the immunotherapy. This led to the identification of a protein that helps tumors evade the immune system, called NR2F6, which was found not only in tumor cells, but also in the surrounding noncancerous cells.

To confirm their findings in mice, the researchers genetically removed the NR2F6 protein in both melanoma tumors and in the tumors’ environment. This inhibited melanoma growth more strongly, compared to when this effect occurs in either the tumor or its microenvironment alone. The cancer’s response to immunotherapy was also enhanced upon loss of NR2F6 in both tumors and their microenvironment. “This tells us that NR2F6 helps melanoma evade the immune system, and without it, the immune system can more readily suppress tumor growth,” explains Hyungsoo Kim, PhD, a research assistant professor at Sanford Burnham Prebys.

To help advance their discovery further, the team is working with the Institute’s Conrad Prebys Center for Chemical Genomics to identify new drugs that can target NR2F6.