Malignant brain tumors are the most common cause of solid cancer death in children. New targeted therapies are vital to improve treatment outcomes, but must be developed to enable trafficking across the blood brain barrier (BBB). Since activated T cells cross the BBB, cancer immunotherapy can be harnessed to unlock the cytotoxic potential of the immune system. However, standard of care treatments (i.e., chemotherapy and radiation) applied concomitant to pediatric brain tumor immunotherapy may abrogate induction of immunotherapeutic responses. This review will discuss the development of immunotherapies within this paradigm using emerging approaches being investigated in phase I/II trials in children with refractory brain tumors, including checkpoint inhibitors, vaccine immunotherapy, and adoptive cell therapy.
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