Natural killer (NK) cells in the human body can kill and contain viruses and cancerous tumors, and a new study from the University of Southern California (USC) describes for the first time how those cells can be manipulated by epigenetics. The discovery, detailed in the Proceedings of the National Academy of Sciences, paves the way for developing more effective cancer drugs.
"Natural killer cells are very attractive targets for immunotherapy because they are able to kill tumor cells," said Si-Yi Chen, M.D., Ph.D., a faculty member of the USC Norris Comprehensive Cancer Center and senior author of the study. "While scientists all around the world are working on developing new drugs using NK cells, none of the drugs in development focuses on epigenetic regulation of the cells. Our study describes how an epigenetic process involving the enzyme MYSM1 plays a critical role in the development of natural killer cells."
Epigenetics involve biochemical changes in the body that directly affect DNA, turning some genes on and turning others off. MYSM1 is an enzyme in the body's immune system that turns genes on and off by modifying proteins called histones embedded in DNA.
Through a series of experiments in mice, Chen and his colleagues demonstrate that MYSM1 is required for natural killer cells to mature and function properly.
"We found that MYSM1 creates access to proteins that enhance gene transcription and, ultimately, the maturation of natural killer cells themselves," said Vijayalakshmi Nandakumar, a Ph.D. student at the Keck School of Medicine of USC and the study's first author. "To date, there are no elaborate reports linking an epigenetic phenomenon to natural killer cell development. More importantly, unlike conventional therapies, NK cell-based therapies have shown to be more effective against metastasis. We believe cancer drugs targeting this pathway could be a viable option for future immunotherapies."
Co-authors include YuChia Chou, Linda Zang and Xue F. Huang, all of the Keck School of Medicine of USC. Their research was supported by National Institutes of Health (grants R01CA090427, AI084811, CA116677, AI068472, CA100841 and AI08185) and by a Leukemia & Lymphoma Society Specialized Center of Research Award.
Article cited: Nandakumar, V., Chou, Y.C., Zang, L., Huang, X.F., & Chen, S.Y. (2013). Epigenetic control of NK cell maturation by histone H2A deubiquitinase MYSM1. Proceedings of the National Academy of Sciences Early Edition, 1-11. Published online Sept. 23, 2013; doi:10.1073/pnas.1308888110
ABOUT USC NORRIS COMPREHENSIVE CANCER CENTER
USC Norris Comprehensive Cancer Center has been leading the fight to make cancer a disease of the past. As one of the eight original comprehensive cancer centers in the United States, its mission is to treat and prevent cancer by advancing and integrating education, research, and personalized patient care. For 40 years, USC Norris has been revolutionizing cancer research with innovative surgical techniques and novel cancer treatments. The cancer center's breakthroughs and discoveries in the field of epigenetics have led the way to a greater understanding of the underlying causes of cancer and new methods of prevention, detection, and treatment. With a multidisciplinary team of more than 250 dedicated scientists and physicians, USC Norris Comprehensive Cancer Center offers patients hope in the battle against cancer.
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Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. Encompassing academic, research and clinical entities, it consists of the Keck School of Medicine of USC, one of the top medical schools in Southern California; the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established in the United States; the USC Care faculty practice; the Keck Medical Center of USC, which includes two acute care hospitals: 411-bed Keck Hospital of USC and 60-bed USC Norris Cancer Hospital; and USC Verdugo Hills Hospital, a 158-bed community hospital. It also includes outpatient facilities in Beverly Hills, downtown Los Angeles, La Cañada Flintridge, Pasadena, and the USC University Park campus. USC faculty physicians and Keck School of Medicine departments also have practices throughout Los Angeles, Orange and Riverside counties.