研究动态
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基于转录组学的儿科低级别胶质瘤免疫基质微环境特征。

Transcriptomics-based characterization of the immuno-stromal microenvironment in pediatric low-grade glioma.

发表日期:2024
作者: Meik Körner, Michael Spohn, Ulrich Schüller, Michael Bockmayr
来源: OncoImmunology

摘要:

免疫治疗选择在低级别胶质瘤中并不常见,尽管这种疗法可能对无法手术和侵袭性病例有益。对低级别胶质瘤中的免疫和基质细胞的了解与此类方法高度相关,但仍需要改进。收集了来自 400 个低级别神经胶质瘤和 193 个高级神经胶质瘤的已发表基因表达数据,使用专门为脑肿瘤设计的反卷积方法来量化 10 个微环境细胞群。首先,我们研究了低级别和高级别胶质瘤微环境的一般差异。低级别和高级别肿瘤分别聚集在一起,并且在这些组内表现出总体相似性和明显差异,主要区别是高级别神经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呈现出最高的总体免疫细胞浸润。对低级别胶质瘤的进一步分析呈现出免疫细胞浸润的三种不同的微环境特征,可分为T细胞/树突状/自然杀伤细胞、中性粒细胞/B谱系/自然杀伤细胞和单核细胞/血管/基质细胞-细胞主导的免疫簇。这些簇与肿瘤位置、年龄和组织学诊断相关,但与性别或无进展生存期无关。生存分析表明,可以根据基因表达、临床数据以及两者与支持向量机的组合来预测预后,并揭示了血管标志物的负预后相关性。总的来说,我们的工作表明,低级别和高级别胶质瘤可以通过免疫细胞浸润来表征和区分。低级别胶质瘤聚集成三种不同的免疫肿瘤微环境,这可能会引起即将进行的免疫治疗研究的进一步兴趣。© 2024 作者。经泰勒许可出版
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.© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.