Funded by Bristol-Myers Squibb
Although childhood cancer survival rates have improved over the past 40 years, pediatric acute myeloid leukemia (AML) is still very difficult to treat successfully. This is partially because the immune system has a hard time recognizing and killing AML cells. Though white blood cells usually fight infections or cancer, certain types of “tumor-permissive” white blood cells (APCs) make it easier for cancer to escape being recognized by the immune system. These tumor-permissive APCs send out signals to other immune cells telling them to relax and not kill leukemia cells. Our research goal is to find ways to make these APCs stop sending tumor-permissive signals, so that the immune system can recognize AML cells better and get rid of the leukemia. Specifically, we found that APCs use a protein called MerTK to send tumor-permissive signals to other immune cells. When we block MerTK using a new orally-active drug, APCs stop sending tumor-permissive signals and instead, start sending new signals that tell other immune cells to fight leukemia. MerTK drugs are headed to clinical trials for their anti-cancer effects; our research demonstrates that these drugs could also be used to boost the immune system against cancer. With this grant, we will investigate the cellular steps involved in blocking MerTK, so that we can determine how to use MerTK inhibitors most effectively to treat pediatric patients with AML. We hope to show that this novel therapy will help improve pediatric AML survival rates and patient’s quality of life.