New research identifies a gene that hides cancerous cells from immunotherapy

A team at the Fred Hutchinson Cancer Research Center has identified a gene that could make sure that immunotherapy treatments, especially checkpoint inhibitors, work for a wider variety of cancer patients. The study, published today in Developmental cell, found that when the DUX4 gene is expressed in cancer cells, it can prevent the cancer from being recognized and destroyed by the immune system.

The team, led by Drs. Robert Bradley and Stephen Tapscott examined the gene expression profiles of nearly 10,000 cancers of 33 different cancer types and found that DUX4, a gene primarily known for its badociation with specific muscular dystrophy (FACS) or FSHD ), systematically presented many different solid tumors, including cancers of the bladder, bad, lung, kidneys and stomach. DUX4 prevented immune cells from recognizing cancer cells, so patients whose cancer expressed the gene were less likely to respond to immunotherapy. Because DUX4 is expressed in many cancers, blocking its activity may increase the success of immune checkpoint inhibitors.

"Immunotherapy can be incredibly powerful against previously incurable cancers, but it's not yet effective for most patients," Bradley said. "Understanding the mechanisms that prevent the immune system from identifying and attacking tumors is a first step toward finding treatments for all cancer patients."

Tapscott, who previously studied the role of DUX4 in early development and in FSHD muscular dystrophy, notes that the findings are an example of how rapid but regulated growth during early development can be reactivated in cancers. as creeping and unregulated cell growth. . DUX4 is normally expressed early in development, when embryonic cells must escape detection by the maternal immune system.

"This study suggests that cancer cells express DUX4 to hijack a normal normal development program that may suppress anti-cancer immune activity," said Tapscott.

Tapscott also notes that there is no increased risk of cancer in people with FSHD, which indicates that cancer cells use DUX4 as a development tool to help reduce the risk of cancer. avoid the immune system, but not as a causative factor of cancer.

Bradley and Tapscott hope that their work will eventually lead to the development of targeted treatments for DUX4, which will improve the success of immunotherapies for a wide range of cancers.