PDF(Pubmed)
Abstract：
Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.
摘要：
在低级别神经胶质瘤中，免疫治疗方案并不常见，尽管此类疗法可能对无法手术和侵袭性病例有益。对低度神经胶质瘤中的免疫和基质细胞的了解与此类方法高度相关，但仍需改进。收集了来自400个低级别神经胶质瘤和193个高级别神经胶质瘤的已发布基因表达数据，以使用明确为脑肿瘤设计的去卷积方法来量化10个微环境细胞群。首先,我们调查了低级别和高级别胶质瘤微环境的一般差异.低级和高级肿瘤聚集在一起，分别,并显示出这些群体之间的总体相似性和明显差异，主要差异是高级别胶质瘤中成纤维细胞和T细胞的浸润较高。在分析的实体中，神经节胶质瘤和多形性黄色星形细胞瘤表现出最高的整体免疫细胞浸润。对低级别神经胶质瘤的进一步分析显示了免疫细胞浸润的三个不同的微环境特征，可以分为T细胞/树突状/自然杀伤细胞-，嗜中性/B谱系/自然杀伤细胞-，和单核细胞/血管/基质细胞为主的免疫簇。这些簇与肿瘤位置相关，年龄,和组织学诊断，但与性别或无进展生存期无关。生存分析显示,可以从基因表达预测预后,临床资料,以及两者与支持向量机的组合，并揭示了血管标志物的负面预后相关性。总的来说,我们的工作表明，低度和高度胶质瘤可以通过其免疫细胞浸润来表征和分化。低级别神经胶质瘤聚集到三个不同的免疫肿瘤微环境中，这可能对即将到来的免疫治疗研究有进一步的兴趣。
