A study reveals a gene that hides tumor 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 The gene is expressed in cancer cells, it can prevent the system 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 types of cancer and found that DUX4, a gene known primarily for its badociation with specific muscular dystrophy (FSD), has always been present in many solid tumors, including cancers of the bladder, bad, lung, kidney and kidney. stomach. DUX4 prevented immune cells from recognizing cancer cells, so that patients whose cancer expressed the gene were less likely to respond to immunotherapy. Because DUX4 is expressed in many cancers, the blockage of its activity could increase the success of immune inhibitors.

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

Dr. Robert Bradley, Fred Hutchinson Cancer Research Center

Tapscott, who previously studied the role of DUX4 in early development and in FSHD muscular dystrophy, the results are an example of how the rapid but regulated growth of early development can be reactivated in cancers as rampant 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 deflect a normal early development program that can suppress anti-cancer immune activity, "Tapscott said.

Tapscott also notes that there is no increased risk of cancer in people with FSHD, indicating that cancer cells use DUX4 as a development tool to avoid the immune system, but not as a driver of cancer.

Bradley and Tapscott hope their work will eventually lead to the development of DUX4Targeted treatments that will improve the success of immunotherapies for a wide range of cancers.