Preclinical Pediatric Brain Tumor Models for Immunotherapy: Hurdles and a Way Forward

Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor. Lower survival rates are partly attributed to the lack of efficacious therapies. The advent and success of immune checkpoint inhibitors (ICIs) in adults have sparked interest in investigating the utility of these therapies alone or in combination with other drug treatments in pediatric patients. However, to achieve improved clinical outcomes, the establishment and selection of relevant and robust preclinical pediatric high-grade brain tumor models is imperative. Here, we review the information that influenced our model selection as we embarked on an international collaborative study to test ICIs in combination with epigenetic modifying agents to enhance adaptive immunity to treat pediatric brain tumors. We also share challenges that we faced and potential solutions.