Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Brain. 2021 Oct 22;144(9):2594-2609. doi: 10.1093/brain/awab155.
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.
在过去的十年中，人们在阐明儿童高级别脑肿瘤的起源和基因组特征方面取得了显著的进展。显然，与成人的高级别脑肿瘤相比，小儿高级别神经胶质瘤在多个方面存在差异，包括：DNA 拷贝数、基因表达谱、中枢神经系统内的肿瘤位置以及体细胞组蛋白突变等遗传改变。尽管取得了这些进展，但针对神经胶质瘤患儿的临床试验历史上一直基于无效的成人方案，这些方案没有考虑到两者之间的基本生物学差异。此外，尽管我们对驱动肿瘤进展的内在细胞机制的认识已经大大扩展，但对于小儿高级别神经胶质瘤中的动态肿瘤免疫微环境知之甚少。在这篇综述中，我们探讨了这些神经胶质瘤的遗传和表观遗传特征，以及这些特征如何导致具有显著生存结果的特定肿瘤亚群的形成。此外，我们对小儿高级别神经胶质瘤肿瘤免疫微环境进行了全面分析，并讨论了旨在利用这些肿瘤的免疫功能的新兴治疗方法。
