Publication date: Apr 03, 2019
Credit: Wikipedia/CC BY-SA 3. 0 Melanomas tend to be “hot” or “cold-if they’re hot, immunotherapy lights melanoma tumors like beacons for elimination by the immune system; but 40-50 percent of melanomas are cold, making them invisible to the immune system, and patients with cold tumors tend to show little benefit from immunotherapies.
Now a University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 identifies a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent.
However, Amato and colleagues including William Robinson, MD, Ph. D., and first author Keith Wells, MD, show that while overall tumor mutation burden may increase the chance of important genetic changes, the immune system’s ability to see tumor tissue may depend more on specific, important changes than on overall mutation burden.
Sixty-seven percent of those responding favorably had alterations in genes associated with the NF-kB signaling pathway, compared with only 19 percent in patients whose tumors did not respond to immunotherapy.
This mutation, G34E, found only in tumors that responded to immunotherapy, has an effect like removing a limiter on NF-kB, allowing increased activation of this pathway.
“Even beyond tumor mutation burden, these specific changes could help doctors predict which melanoma patients will respond and which patients will not respond to anti-PD1 immunotherapies,” Amato says.
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