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Ze'ev Ronai, Ph.D., professor in the Tumor Initiation and Maintenance Program at Sanford Burnham Prebys Medical Discovery Institute and senior author of the study. Credit: Sanford Burnham Prebys Medical Discovery Institute

Scientists at Sanford Burnham Prebys Medical Discovery Institute have demonstrated the therapeutic potential of PRMT5 inhibitors to sensitize unresponsive melanoma to immune checkpoint therapy. PRMT5 inhibitors are currently in clinical trials in oncology, and this research provides a strong rationale for evaluating the drugs in tumors that are not responsive to immune checkpoint therapy. The study was published in Science Translational Medicine.

"Our study reveals that PRMT5 enables tumors to hide from the immune system by controlling two immune signaling pathways," says Ze'ev Ronai, Ph.D., professor in the Tumor Initiation and Maintenance Program at Sanford Burnham Prebys and senior author of the study. "We found that inhibiting PRMT5 enhances both antigen presentation and the activation of innate immunity, prerequisites for effective immune checkpoint therapy. We are optimistic that this research will lead to a near-term, much-needed breakthrough for people with tumors that do not respond to checkpoint inhibitor therapy."

Immunotherapy, which harnesses the power of an individual's immune system to destroy tumors, has revolutionized the treatment of certain cancers. For some people with advanced melanoma, the treatment has extended survival to years instead of months. However, immunotherapy only works for about 40% of people with advanced melanoma. Scientists are working to uncover new approaches that would make the treatment effective for more people with more cancer types.