Epigenetic Regulation of T cell Activation and Immunotherapy
Background
One reason cancer cells grow uncontrollably is because they turn off genetic brakes on growth using a process called DNA methylation. Drugs that block DNA methylation appear to stop cancer from growing and make it more sensitive to other treatments. However, little is known about the impact of these drugs on the normal immune system.
The enzymes that cause DNA methylation are expressed at high levels in T cells of the immune system after activation but only a few genes they turn off are known. We have shown that blocking these enzymes in T cells changes the type of immune response in a way that may help the immune system to destroy cancer cells.
Project Goals
My project seeks to understand:
1) How DNA methylation limits T cell killing of tumor cells, and
2) How blocking DNA methylation can improve cancer vaccines to treat pediatric cancers.
We predict blocking a key DNA methylation enzyme will improve vaccine responses in mice and allow us to identify new genes that are turned off in T cells by DNA methylation. We will use this knowledge to improve the effect of cancer-specific tumor vaccines by giving them in combination with drugs that block DNA methylation.
