Abstract
Over the past decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumours. It has become evident that paediatric high-grade gliomas differ from those in adults with respect to multiple defining aspects including: DNA copy number, gene expression profiles, tumour locations within the CNS and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with gliomas 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 tumour progression has considerably expanded, little is known about the dynamic tumour immune microenvironment in paediatric high-grade gliomas. In this review, we explore the genetic and epigenetic landscape of these gliomas and how this drives the creation of specific tumour subgroups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the paediatric high-grade glioma tumour immune microenvironment and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumours.
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