For the first time, a new study from the Keck School of Medicine of USC has described how natural killer (NK) cells in the human body, which can kill and contain viruses and cancerous tumors, 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, professor of molecular microbiology and immunology at the Keck School, senior author of the study and faculty member of the USC Norris Comprehensive Cancer Center. “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 demonstrated that MYSM1 is required for NK 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 PhD student at the Keck School 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 included YuChia Chou, Linda Zang and Xue Huang, all of the Keck School. The research was supported by the National Institutes of Health (grants R01CA090427, AI084811, CA116677, AI068472, CA100841 and AI08185) and by a Leukemia & Lymphoma Society Specialized Center of Research Award.