Enhancing Effectiveness of Immune Checkpoint Therapy in Neuroblastoma
Treatment for children with high-risk neuroblastoma has improved significantly in the past 20 years; however over half the patients continue to have their disease recur. Improving therapies for neuroblastoma requires us to have a better understanding of the biology of the tumors and the response of the body's immune system to residual tumors that may remain after chemotherapy. Recently, a class of novel therapies directed at re-educating the immune system has shown tremendous benefit in adult cancer. These therapies called immune checkpoint blockade therapy remove the brake placed upon immune cells that are in charge of killing tumor cells. However, these therapies by themselves can cure only a certain portion of adults and are being evaluated in pediatric trials to assess their safety.
Our research has identified a group of immune cells called macrophages that are trained by tumor cells to aid them in escaping immune-related death and promote their growth. We believe these cells perform their function through the immune checkpoint system and thus contribute to the resistance observed to immune checkpoint blockade therapies in adults.
In our proposal, we utilize murine models of neuroblastoma (mice that develop neuroblastoma) to study the development of resistance to immunotherapy and test novel drugs to overcome this resistance. We anticipate that our approach would allow development of combination therapies directed against macrophages and immune checkpoints that would be effective in treatment of children with high-risk neuroblastoma.