Recent work has highlighted the tumor microenvironment as a central player in cancer. In particular, interactions between tumor and immune cells may help drive the development of brain tumors such as glioblastoma multiforme (GBM). Despite significant research into the molecular classification of glioblastoma, few studies have characterized in a comprehensive manner the immune infiltrate in situ and within different GBM subtypes.In this study, we use an unbiased, automated immunohistochemistry-based approach to determine the immune phenotype of the four GBM subtypes (classical, mesenchymal, neural and proneural) in a cohort of 98 patients. Tissue Micro Arrays (TMA) were stained for CD20 (B lymphocytes), CD5, CD3, CD4, CD8 (T lymphocytes), CD68 (microglia), and CD163 (bone marrow derived macrophages) antibodies. Using automated image analysis, the percentage of each immune population was calculated with respect to the total tumor cells. Mesenchymal GBMs displayed the highest percentage of microglia, macrophage, and lymphocyte infiltration. CD68+ and CD163+ cells were the most abundant cell populations in all four GBM subtypes, and a higher percentage of CD163+ cells was associated with a worse prognosis. We also compared our results to the relative composition of immune cell type infiltration (using RNA-seq data) across TCGA GBM tumors and validated our results obtained with immunohistochemistry with an external cohort and a different method. The results of this study offer a comprehensive analysis of the distribution and the infiltration of the immune components across the four commonly described GBM subgroups, setting the basis for a more detailed patient classification and new insights that may be used to better apply or design immunotherapies for GBM.

中文翻译：

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与不同的胶质母细胞瘤分子亚型相关的免疫景观。

最近的工作突出了肿瘤微环境在癌症中的重要作用。特别是，肿瘤与免疫细胞之间的相互作用可能有助于推动脑部肿瘤如多形性胶质母细胞瘤（GBM）的发展。尽管对胶质母细胞瘤的分子分类进行了大量研究，但很少有研究以全面的方式对免疫原位和不同GBM亚型内的浸润进行表征。在这项研究中，我们使用基于无偏倚，自动化免疫组织化学的方法来确定胶质母细胞瘤的免疫表型。 98名患者中的4种GBM亚型（经典，间质，神经和前神经）。对组织微阵列（TMA）的CD20（B淋巴细胞），CD5，CD3，CD4，CD8（T淋巴细胞），CD68（小胶质细胞）和CD163（骨髓衍生的巨噬细胞）抗体染色。使用自动图像分析，计算每个免疫种群相对于总肿瘤细胞的百分比。间充质GBMs显示出最高百分比的小胶质细胞，巨噬细胞和淋巴细胞浸润。在所有四个GBM亚型中，CD68 +和CD163 +细胞是最丰富的细胞群，而CD163 +细胞的百分比越高，预后越差。我们还比较了我们的结果与TCGA GBM肿瘤中免疫细胞类型浸润的相对组成（使用RNA-seq数据），并验证了使用外部队列和其他方法通过免疫组织化学获得的结果。这项研究的结果全面分析了GBM四个亚组中免疫成分的分布和浸润，