Immune checkpoint inhibitors in medulloblastoma: current updates in preclinical and clinical developments.
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Medulloblastoma (MB) is the most common pediatric embryonal tumor of the central nervous system. MB grows rapidly in the cerebellum and causes devastating disease in young children. The presence of high-risk molecular or histopathological features is associated with frequent recurrence, resistance to therapy, and poor prognosis, with few experiencing long-term survival. The current standard of care for MB includes surgical resection, radiation, and chemotherapy; however, there remains a need for more specific and effective treatment strategies, especially in recurrent disease. Promising developments in immune checkpoint inhibition have recently entered clinical trials, yet few address MB. Classic immune checkpoints such as Programmed Cell Death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have recently been identified as potential therapeutic targets for slowing MB progression in the recurrent setting. Preclinical and clinical studies have identified additional targets such as B7-H3, V-domain Ig Suppressor of T-cell Activation (VISTA), lymphocyte-activated gene 3 (LAG-3), P-selectin glycoprotein 1 (PSGL-1), and T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) expression in the MB TME. This review summarizes current preclinical and clinical prospects for immune checkpoint inhibition via direct antibody targeting for the treatment of MB and describes the proposed next generation of immune checkpoint inhibitors.