Immune cell gene expression signatures in diffuse glioma are associated with IDH mutation status, patient outcome and malignant cell state, and highlight the importance of specific cell subsets in glioma biology.
Immune cell gene expression signatures in diffuse glioma are associated with IDH mutation status, patient outcome and malignant cell state, and highlight the importance of specific cell subsets in glioma biology.
复制标题
弥漫性神经胶质瘤中的免疫细胞基因表达特征与IDH突变状态，患者结局和恶性细胞态有关，并突出了特定细胞亚群在神经胶质瘤生物学中的重要性。
DOI：
10.1186/s40478-022-01323-w
复制
发表时间：
2022-02-10
影响因子：
7.1
通讯作者：
Aldape K
中科院分区：
文献类型：
--
作者：
Mehani B;Asanigari S;Chung HJ;Dazelle K;Singh A;Hannenhalli S;Aldape K
肿瘤微环境（TME）在包括胶质瘤在内的各种癌症中发挥着重要作用。我们使用CIBERSORTx和LM 22/LM 10血液免疫特征在3个大型临床注释的胶质瘤数据集中估计了免疫细胞类型特异性基因表达谱，发现特定免疫细胞的比例和估计的基因表达模式根据IDH突变状态显着变化。当分别考虑IDH-WT和IDH-MUT肿瘤时，免疫细胞基因表达的聚类分析确定了具有不同生存结果的组。我们通过将来自19个胶质瘤肿瘤样本的单细胞RNA测序数据的特征矩阵应用于批量分析数据，验证了LM 22/LM 10结果的发现，从而证实并扩展了这些发现。为了将免疫细胞特征与检查点治疗的结果联系起来，我们随后显示了单核细胞谱系细胞基因表达簇与患者生存率和间充质基因表达评分的显著相关性。将基于免疫细胞的基因表达与先前描述的胶质瘤中的恶性细胞状态整合证明，巨噬细胞M0丰度与IDH-WT胶质瘤中的间充质状态显著相关，有证据表明以前涉及的抑瘤素-M受体和巨噬细胞在间充质状态中的作用。在富含间充质细胞状态的IDH-WT肿瘤中，估计的MO巨噬细胞表达特征也协调地趋向于间充质特征。我们还检查了按1 p/19 q状态分层的IDH-MUT肿瘤，显示间充质基因表达特征M0巨噬细胞部分在IDH-MUT非共缺失肿瘤中富集。总体而言，这些结果突出了与IDH突变状态、患者预后和弥漫性胶质瘤间质状态相关的免疫细胞环境的生物学和临床意义。在线版本包含补充材料，可通过10.1186/s40478-022-01323-w获得。
The tumor micro-environment (TME) plays an important role in various cancers, including gliomas. We estimated immune cell type-specific gene expression profiles in 3 large clinically annotated glioma datasets using CIBERSORTx and LM22/LM10 blood-based immune signatures and found that the proportions and estimated gene expression patterns of specific immune cells significantly varied according to IDH mutation status. When IDH-WT and IDH-MUT tumors were considered separately, cluster-of-cluster analyses of immune cell gene expression identified groups with distinct survival outcomes. We confirmed and extended these findings by applying a signature matrix derived from single-cell RNA-sequencing data derived from 19 glioma tumor samples to the bulk profiling data, validating findings from the LM22/LM10 results. To link immune cell signatures with outcomes in checkpoint therapy, we then showed a significant association of monocytic lineage cell gene expression clusters with patient survival and with mesenchymal gene expression scores. Integrating immune cell-based gene expression with previously described malignant cell states in glioma demonstrated that macrophage M0 abundance significantly correlated with mesenchymal state in IDH-WT gliomas, with evidence of a previously implicated role of the Oncostatin-M receptor and macrophages in the mesenchymal state. Among IDH-WT tumors that were enriched for the mesenchymal cell state, the estimated M0 macrophage expression signature coordinately also trended to a mesenchymal signature. We also examined IDH-MUT tumors stratified by 1p/19q status, showing that a mesenchymal gene expression signature the M0 macrophage fraction was enriched in IDH-MUT, non-codeleted tumors. Overall, these results highlight the biological and clinical significance of the immune cell environment related to IDH mutation status, patient prognosis and the mesenchymal state in diffuse gliomas. The online version contains supplementary material available at 10.1186/s40478-022-01323-w.
登录
查看更多内容
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
通过免疫基因组分析观察黑色素瘤肿瘤浸润免疫细胞与总生存率的相关性
影响因子：
4
作者：
Huang L;Chen H;Xu Y;Chen J;Liu Z;Xu Q
通讯作者：
Xu Q
DOI：
10.1186/s12964-016-0160-z
发表时间：
2017-01-05
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Catakovic K;Klieser E;Neureiter D;Geisberger R
通讯作者：
Geisberger R
影响因子：
3.8
作者：
Ascierto, Maria Libera;Kmieciak, Maciej;Idowu, Michael O.;Manjili, Rose;Zhao, Yingdong;Grimes, Margaret;Dumur, Catherine;Wang, Ena;Ramakrishnan, Viswanathan;Wang, Xiang-Yang;Bear, Harry D.;Marincola, Francesco M.;Manjili, Masoud H.
通讯作者：
Manjili, Masoud H.
影响因子：
50.3
作者：
Hara T;Chanoch-Myers R;Mathewson ND;Myskiw C;Atta L;Bussema L;Eichhorn SW;Greenwald AC;Kinker GS;Rodman C;Gonzalez Castro LN;Wakimoto H;Rozenblatt-Rosen O;Zhuang X;Fan J;Hunter T;Verma IM;Wucherpfennig KW;Regev A;Suvà ML;Tirosh I
通讯作者：
Tirosh I