Abstract
Over the last decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumors. It has become evident that pediatric high-grade gliomas (pHGGs) differ from adult HGGs with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumor locations within the central nervous system, and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with glioma have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumor progression has considerably expanded, little is known concerning the dynamic tumor immune microenvironment (TIME) in pHGGs. In this review, we explore the genetic and epigenetic landscape of pHGGs and how this driv es the creation of specific tumor sub-groups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the pHGG TIME and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumors.
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