Pediatric brain tumors are the most common solid tumors in children, with 5,000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0-14 years are pediatric high-grade gliomas (pHGGs). pHGG is the deadliest cancer in children, with the median survival time of only 12-15 months despite aggressive therapy. pHGGs show distinct features from their adult counterpart (adult high-grade gliomas), and no new therapy for the disease has been developed for over 3 decades. Various high frequent mutations have been discovered in pHGGs, which potentially could be recognized by the immune system. However, the immune system in those patients has been disabled by a u...

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Pediatric brain tumors are the most common solid tumors in children, with 5,000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0-14 years are pediatric high-grade gliomas (pHGGs). pHGG is the deadliest cancer in children, with the median survival time of only 12-15 months despite aggressive therapy. pHGGs show distinct features from their adult counterpart (adult high-grade gliomas), and no new therapy for the disease has been developed for over 3 decades. Various high frequent mutations have been discovered in pHGGs, which potentially could be recognized by the immune system. However, the immune system in those patients has been disabled by a unique type of cell in their brains, so that the cancer cells cannot be recognized by the immune system anymore. To make things worse, due to certain defects in these cells, they have turned themselves from attackers of cancer cells to helpers of cancer cells. Thus, there persists an urgent clinical need to uncover mechanism-based therapeutic avenues against pHGGs by targeting these unique immune cells. Our previous work has identified a class of important molecular regulators for these immune cells in pHGGs, and we have also found that two potent and safe drugs that were developed for other diseases could effectively fix these cells and make the immune system able to recognize and attack cancer cells again. Our proposal will help us further understand how these drugs achieve their functions of fixing the immune system and develop better therapeutic approaches by combining with other types of immunotherapies.

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