Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.
Transcriptional immunogenomic analysis reveals distinct immunological clusters in paediatric nervous system tumours.
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DOI：
10.1186/s13073-023-01219-x
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发表时间：
2023-09-07
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
--
作者：
癌症免疫疗法，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应答率，这突出表明需要为患者选择建立稳健的生物标志物。虽然成人肿瘤微环境已被广泛研究，以描绘免疫应答的决定因素，但儿科实体瘤的免疫组成仍然相对不确定，需要进行研究以确定潜在的免疫生物标志物。为了告知胚胎起源的儿科癌症的免疫治疗方法，我们对来自三个公开数据集的925个未经治疗的儿科神经系统肿瘤（pedNST）的RNA-seq数据进行了免疫基因组学分析，这些肿瘤跨越了12种癌症类型。在pedNST中，我们发现了四个广泛的免疫簇：儿科炎症（10%），髓样占主导地位（30%），免疫中性（43%）和免疫沙漠（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来验证这些聚类。我们报告了这些免疫簇在癌症类型内和癌症类型之间的共同生物学，以及特定免疫细胞频率以及T细胞和B细胞库的特征。我们发现免疫浸润水平和肿瘤突变负荷之间没有关联，尽管分子癌症实体在特定的免疫簇中富集。鉴于pedNST内免疫浸润的异质性，我们的研究结果表明，需要个性化的免疫基因组学分析来指导免疫策略的选择。在线版本包含补充材料，可通过10.1186/s13073-023-01219-x获得。
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. The online version contains supplementary material available at 10.1186/s13073-023-01219-x.
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影响因子：
82.9
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影响因子：
30.8
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影响因子：
5.6
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Melisi D
影响因子：
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