Checkpoint immunotherapy has improved outcomes in variety of cancer types, however, they still only work for a fraction of patients. One reason for this appears to be that these immunotherapies only reactivate “killer” T cells temporarily, due to a phenomenon known as epigenetics, which determines how easily certain genes can be turned “on” or “off.” To overcome this, Dr. Ma is investigating how we might target “killer” T cell epigenetics to help improve the durability of their activity against tumors.
Specifically, she is characterizing how metabolism influences the epigenetic states of “killer” T cells, and her team has already found that supplementing them with a building block known as acetate can effectively reprogram and enhance “killer” T cell activity. Now, her goal is to elucidate how to sensitize “killer” T cells to immunotherapies and fully rejuvenate their anti-tumor capacity through a combination of immunotherapy and metabolism-based treatments. In pursuing these studies, Ma hopes to discover new ways to revive the tumor-killing function of our immune system and to discover new drug targets for the treatment of cancer.
Projects and Grants
Metabolic control of epigenetic states that drive CD8 T cell exhaustion and anti-tumor immunity
Salk Institute for Biological Studies | All Cancers | 2020 | Susan Kaech, Ph.D.
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