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Immune checkpoint inhibitors have successfully generated durable responses in melanoma. Ipilimumab and tremelimumab are anti-CTLA4 antibodies that release T cells from a natural inhibitory signal generated through that receptor, resulting in T-cell-mediated tumor killing. How to identify likely responders has been unclear, and how these immune therapies incite a T-cell response is unknown. Snyder and colleagues report major progress in answering these questions. They performed exome sequencing on a set of stage IV melanomas from 11 responders and 14 nonresponders to anti-CTLA4 therapy.
The correlation between overall mutational load and response was strongly significant. Patients whose tumors contained >100 nonsynonymous changes (those that …