PDF(Pubmed)
Abstract：
With the success of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important; however in pediatric brain tumors this remains poorly characterized. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of 1382 samples with detailed clinical and molecular annotation. In low-grade gliomas we identify distinct patterns of immune activation with prognostic significance in BRAF V600E-mutant tumors. In high-grade gliomas, we observe immune activation and T-cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In mismatch repair deficient high-grade gliomas, we find that high tumor inflammation signature is a significant predictor of response to immune checkpoint inhibition, and demonstrate the potential for multimodal biomarkers to improve treatment stratification. Importantly, while overall patterns of immune activation are observed for histologically and genetically defined tumor types, there is significant variability within each entity, indicating that the TIME must be evaluated as an independent feature from diagnosis. In sum, in addition to the histology and molecular profile, this work underscores the importance of reporting on the TIME as an essential axis of cancer diagnosis in the era of personalized medicine.
摘要：
随着癌症免疫治疗的成功，了解肿瘤免疫微环境（TIME）已变得越来越重要;然而，在小儿脑肿瘤中，这仍然不明确。因此，我们开发了一种临床免疫肿瘤学基因表达检测方法,并使用该方法对1382个不同范围的样本进行了分析,并提供了详细的临床和分子注释.在低级别神经胶质瘤中，我们确定了在BRAFV600E突变肿瘤中具有预后意义的免疫激活的不同模式。在高级别神经胶质瘤中，我们观察到肿瘤中的免疫激活和T细胞浸润，这些肿瘤历来被认为是免疫感冒，以及炎症水平的基因组相关性。在错配修复缺陷的高级别神经胶质瘤中，我们发现，高肿瘤炎症特征是免疫检查点抑制反应的重要预测指标，并证明了多模式生物标志物改善治疗分层的潜力。重要的是,虽然在组织学和基因定义的肿瘤类型中观察到免疫激活的总体模式，每个实体内部都有很大的可变性，表明必须将TIME评估为独立于诊断的特征。总之,除了组织学和分子特征，这项工作强调了在个性化医疗时代报告时间作为癌症诊断的重要轴的重要性.
