It is recognized that the tumor microenvironment (TME) plays a critical role in the biology of cancer. To better understand the role of immune cell components in CNS tumors, we applied a deconvolution approach to bulk DNA methylation array data in a large set of newly profiled samples (n = 741) as well as samples from external data sources (n = 3311) of methylation-defined glial and glioneuronal tumors. Using the cell-type proportion data as input, we used dimensionality reduction to visualize sample-wise patterns that emerge from the cell type proportion estimations. In IDH-wildtype glioblastomas (n = 2,072), we identified distinct tumor clusters based on immune cell proportion and demonstrated an association with oncogenic alterations such as EGFR amplification and CDKN2A/B homozygous deletion. We also investigated the immune cluster-specific distribution of four malignant cellular states (AC-like, OPC-like, MES-like and NPC-like) in the IDH-wildtype cohort. We identified two major immune-based subgroups of IDH-mutant gliomas, which largely aligned with 1p/19q co-deletion status. Non-codeleted gliomas showed distinct proportions of a key genomic aberration (CDKN2A/B loss) among immune cell-based groups. We also observed significant positive correlations between monocyte proportion and expression of PD-L1 and PD-L2 (R = 0.54 and 0.68, respectively). Overall, the findings highlight specific roles of the TME in biology and classification of CNS tumors, where specific immune cell admixtures correlate with tumor types and genomic alterations.

中文翻译：

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大量 DNA 甲基化数据的免疫细胞反卷积揭示了神经胶质/神经元肿瘤中甲基化类别、关键体细胞改变和细胞状态的关联


人们认识到肿瘤微环境（TME）在癌症生物学中起着至关重要的作用。为了更好地了解免疫细胞成分在 CNS 肿瘤中的作用，我们对大量新分析样本 (n = 741) 以及来自外部数据源的样本 (n = 3311) 中的大量 DNA 甲基化阵列数据应用了反卷积方法。甲基化定义的胶质细胞和胶质神经元肿瘤。使用细胞类型比例数据作为输入，我们使用降维来可视化从细胞类型比例估计中出现的样本模式。在 IDH 野生型胶质母细胞瘤 (n = 2,072) 中，我们根据免疫细胞比例识别出不同的肿瘤簇，并证明与 EGFR 扩增和 CDKN2A/B 纯合缺失等致癌改变相关。我们还研究了 IDH 野生型队列中四种恶性细胞状态（AC 样、OPC 样、MES 样和 NPC 样）的免疫簇特异性分布。我们确定了 IDH 突变神经胶质瘤的两个主要的基于免疫的亚组，它们在很大程度上与 1p/19q 共缺失状态一致。非编码缺失神经胶质瘤在基于免疫细胞的群体中表现出不同比例的关键基因组畸变（CDKN2A/B 丢失）。我们还观察到单核细胞比例与 PD-L1 和 PD-L2 表达之间存在显着的正相关性（R 分别 = 0.54 和 0.68）。总体而言，这些发现强调了 TME 在 CNS 肿瘤生物学和分类中的特定作用，其中特定的免疫细胞混合物与肿瘤类型和基因组改变相关。