Dev cell: discover a new mechanism for cancer cells to charm immune cells! Let cancer cells in the body unimpeded!

July 25, 2019 / BIOON / - a team at Fred Hutchinson Cancer Research Center has identified a gene that enables immunotherapy, particularly checkpoint inhibitors, to work in a wider range of cancer patients When dux4 gene is expressed in cancer cells, it can prevent cancer cells from being recognized and damaged by the immune system The team, led by Dr Robert Bradley and Stephen Tapscott, looked at gene expression in tumor tissues of nearly 10000 patients with 33 different cancers and found that dux4, a gene associated with specific muscular dystrophy, facioscapulohumeral muscular dystrophy, is expressed in many solid tumors, including bladder, breast, lung, kidney and stomach cancer Dux4 prevents immune cells from recognizing cancer cells, so when cancer patients express the gene, they are less responsive to immunotherapy Because dux4 is expressed in many cancers, blocking its activity may increase the success of immunocheckpoint inhibitors Photo source: http://cn.bing.com Bradley said: "immunotherapy may be very effective for previously incurable cancer, but it has no effect for most patients Understanding the mechanisms that prevent the immune system from recognizing and attacking tumors is the first step in finding treatments for all cancer patients "Tapscott has previously studied the role of dux4 in early development and FSHD muscular dystrophy, pointing out that these findings are an example of how rapid but regulated growth in early development can be reactivated in rampant and unregulated cancer cell growth Dux4 is usually expressed during early development, when embryonic cells need to avoid detection of the maternal immune system "This study shows that cancer cells express dux4 in order to hijack a normal early development program that inhibits cancer immune activity," Tapscott said "Tapscott further points out that there is no increase in cancer risk in FSHD patients, suggesting that cancer cells use dux4 as a development tool to avoid the immune system, but it is not a driver of cancer Tapscott and Bradley hope that their work will eventually lead to the development of treatments for dux4, thereby increasing the success rate of immunotherapy for multiple cancers Reference: Guo Liang check et al, dux4 supplies MHC class I to promote cancer immune evolution and resistance to checkpoint blockade, developmental cell (2019) Doi: 10.1016/j.devcel.2019.06.011