癌症免疫治疗（包括免疫检查点抑制剂和嵌合抗原受体（CAR）T细胞疗法）在儿科患者中显示出不同的响应率，凸显了建立坚实的生物标志物用于病人选择的必要性。虽然成年人的肿瘤微环境已广泛研究以确定免疫反应的决定因素，但儿童实体肿瘤的免疫组成相对未被充分描述，因此需要进行调查以鉴定潜在的免疫生物标志物。为了了解身源性儿科癌症的免疫治疗方法，我们对来自三个公开可用数据集的12种癌症类型的925个儿科神经系统肿瘤（pedNST）的RNA测序数据进行了免疫基因组分析。在pedNST中，我们发现了四个宽泛的免疫簇：儿童激活（10％），髓系细胞为主（30％），免疫中性（43％）和免疫贫瘠（17％）。我们使用免疫组织化学、甲基化免疫推断和组织图像的分割分析验证了这些簇。我们报告了这些免疫簇在癌症类型内部和跨癌症类型的共享生物学，以及特定免疫细胞频率以及T细胞和B细胞的复制库的特征。我们发现，免疫浸润水平与肿瘤突变负担之间没有关联，尽管特定免疫簇内富含分子癌症实体。鉴于pedNST的免疫浸润的异质性，我们的发现表明需要个体化免疫基因组分析来指导免疫治疗策略的选择。 © 2023. BioMed Central Ltd., part of Springer Nature.

Cancer immunotherapies including immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR) T-cell therapy have shown variable response rates in paediatric patients highlighting the need to establish robust biomarkers for patient selection. While the tumour microenvironment in adults has been widely studied to delineate determinants of immune response, the immune composition of paediatric solid tumours remains relatively uncharacterized calling for investigations to identify potential immune biomarkers.To inform immunotherapy approaches in paediatric cancers with embryonal origin, we performed an immunogenomic analysis of RNA-seq data from 925 treatment-naïve paediatric nervous system tumours (pedNST) spanning 12 cancer types from three publicly available data sets.Within pedNST, we uncovered four broad immune clusters: Paediatric Inflamed (10%), Myeloid Predominant (30%), Immune Neutral (43%) and Immune Desert (17%). We validated these clusters using immunohistochemistry, methylation immune inference and segmentation analysis of tissue images. We report shared biology of these immune clusters within and across cancer types, and characterization of specific immune cell frequencies as well as T- and B-cell repertoires. We found no associations between immune infiltration levels and tumour mutational burden, although molecular cancer entities were enriched within specific immune clusters.Given the heterogeneity of immune infiltration within pedNST, our findings suggest personalized immunogenomic profiling is needed to guide selection of immunotherapeutic strategies.© 2023. BioMed Central Ltd., part of Springer Nature.