Immune cells in a majority of people with melanoma fail to respond properly to interferon, which normally activates the immune system, report scientists at the Stanford University School of Medicine. "We think this is a dominant way that immune dysfunction occurs in people with cancer," says senior author, Peter Lee, M.D., associate professor of medicine.
The group started by separating the four major types of immune cells from melanoma patients and healthy people. They then looked compares the sets of immune cells to see if they had the same levels of activation of roughly 20,000 genes.
The investigators found that the B cells and both types of T cells in people with melanoma showed activity levels that differed from healthy people in only 25 of those genes. Of those 25, 17 were normally turned on in response to interferon.
To verify that the interferon signaling was defective in people with melanoma, the researchers isolated those cells and exposed them to interferon. As predicted, immune cells from people with melanoma also failed to respond normally to the immune activation signal. However, the researchers found that if they left the cells in the presence of a high dose of interferon for much longer than would normally be required, those cells did begin responding.
Dr. Lee says the finding explains why a common melanoma treatment, in which some doctors have treated patients with prolonged exposure to interferon, sometimes helps. "Doctors knew it worked in some people but didn't know why."
The study will be published in the May issue of Public Library of Science-Medicine.