Molecular Cell: DNA hypomethylating agents increase activation and cytolytic act
Posted by beauty33 on March 31st, 2022
In a new study, researchers from the Princess Margaret Cancer Center of the Canadian University Medical Network and the University of Toronto improved anti-tumor responses by carrying out a series of elegant experiments to construct \"super soldiers\" with specific leukocytes. Specifically, they describe an epigenetic therapy that modifies DNA and can convert killer T cells into \"super soldiers\" by enhancing their ability to kill cancer cells. The results were published in Molecular Cell, entitled \"DNA hypomethylating agents increase activation and cytolytic activity of CD8 + T cells\". The corresponding author of the paper is Dr. Daniel D. De Carvalho of Princess Margaret Cancer Center. The first author of the paper is Helen Loo Yau, PhD student at Princess Margaret Cancer Center, and Dr. Emma Bell, postdoctoral researcher.
Their findings may enhance immunotherapy, a new model of cancer treatment that is currently effective for a small number of cancer patients. Some patients respond well to immunotherapy with dramatic reduction in tumor size, but others respond only partially or not at all. Clinicians and scientists around the world are trying to understand why immunotherapy is only helpful for some patients.
These researchers, interested in this finding, set out to apply this epigenetic DNA-modifying therapy directly to T cells in the laboratory. They isolated T cells from healthy human donors as well as patients with melanoma, breast, ovarian, and colorectal cancers. Their results demonstrate that this epigenetic therapy enhances the cancer-killing ability of these T cells.
High-dimensional single-cell mass cytometry analysis—a new generation of technology that can dissect single-cell and drug responses—has found that T cells increase the number of granzyme and perforin proteins used to perform killing function. When granzymes and perforin are released, like a fatal special police force, perforin is able to punch holes in the cell membrane and allow granzymes to enter infected cells or cancer cells and complete the task of killing these cells.
This emerging field of epigenetic therapy aims to influence genetic activity without actually modifying the sequence of DNA, thus making it an exciting therapeutic avenue for cancer research.
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