A crucial signaling pathway that can tell the immune system to fight off cancer can also be co-opted by cancer cells to put the brakes on the immune system, according to a new study from researchers in the Abramson Cancer Center. Researchers say this increased understanding can serve as a biomarker that helps predict which patients are likely to respond to immunotherapies. They also show how tipping the balance has potential implications for therapy itself, since blocking the signal in cancer cells helps the immune system fight off tumors in multiple pre-clinical cancer models. The study was published in the journal Cell.
The study focused on the interferon (IFN) signaling pathway. Interferons normally help activate the immune system to protect cells from viruses and get their name because they literally interfere with a virus’ ability to spread. However, IFNs can also put the brakes on the immune system.
“This paradoxical effect has been seen in other diseases—such as chronic viral infections—but our study shows how cancer cells take advantage of the suppressive properties of IFNs to interfere with cancer immunotherapy,” says the study’s senior author Andy J. Minn, an associate professor of radiation oncology and director of The Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation.
For the current study, researchers found when IFNs put a brake on the immune system, cancer cells intercept and manipulate that signal. However, when IFNs are allowed to send signals to the immune system, immune cells are able to do their jobs and kill tumors. Understanding this balance of how IFN signals are routed to immune versus cancer cells could provide a biomarker for whether immunotherapy can be effective.
“If we know the signaling is tilted toward immune cells or toward cancer, we may be able to better predict if a patient is likely to respond,” Minn says.
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