Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Central Nervous System Unit, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
J Neurooncol. 2023 Aug;164(1):211-220. doi: 10.1007/s11060-023-04406-3. Epub 2023 Aug 6.
Resection of high-grade gliomas has been considerably improved by 5-aminolevulinic acid (5-ALA). However, not all neurobiological properties of 5-ALA are fully understood. Specifically, potential differences in immune infiltration have not been conclusively examined, despite recent reports that immune cells might play a role. Thus, we here provide a systematic mapping of immune infiltration of different 5-ALA fluorescence levels.
Tumor-associated macrophages (CD68, CD163), cytotoxic T cells (CD8), and regulatory T cells (FoxP3) were quantified via three methods. First, data from The Cancer Genome Atlas (TCGA) of 172 patients was examined for correlations between 5-ALA fluorescence-related mRNA expression signatures and immune markers. Second, as classical histology, 508 stained slides from 39 high-grade glioma patients were analysed semi-quantitatively by two independent reviewers, generating 1016 data points. Third, digital image analysis was performed with automated scanning and algorithm-based cell quantification.
TCGA mRNA data from 172 patients showed a direct, significant correlation between 5-ALA signatures and immune markers (p < 0.001). However, we were not able to confirm this finding in the here studied initial set of 39 patient histologies where we found a comparable immune infiltration in different fluorescence levels. Digital image analysis correlated excellently with standard histology.
With mapping the immune infiltration pattern of different 5-ALA categories, we are adding fundamental basic insights to the field of 5-ALA and glioma biology. The observation that a significant correlation in TCGA data did not fully translate to detectable differences in immune infiltration in first histology data warrants further investigation in larger cohorts.
5-氨基酮戊酸（5-ALA）的使用极大地提高了高级别神经胶质瘤的切除率。然而，人们对 5-ALA 的许多神经生物学特性仍不完全了解。特别是，尽管最近有报道称免疫细胞可能发挥作用，但尚未明确检查潜在的免疫浸润差异。因此，我们在此提供了不同 5-ALA 荧光水平下免疫浸润的系统图谱。
通过三种方法对肿瘤相关巨噬细胞（CD68、CD163）、细胞毒性 T 细胞（CD8）和调节性 T 细胞（FoxP3）进行定量。首先，对 172 名患者的癌症基因组图谱（TCGA）数据进行检查，以分析 5-ALA 荧光相关 mRNA 表达特征与免疫标志物之间的相关性。其次，作为经典组织学，由两名独立的审阅者对半定量分析了 39 名高级别脑肿瘤患者的 508 张染色切片，共生成 1016 个数据点。第三，通过自动扫描和基于算法的细胞定量进行数字图像分析。
来自 172 名患者的 TCGA mRNA 数据显示 5-ALA 特征与免疫标志物之间存在直接、显著的相关性（p<0.001）。然而，我们无法在最初研究的 39 名患者组织学中证实这一发现，因为我们在不同荧光水平下发现了类似的免疫浸润。数字图像分析与标准组织学相关性极佳。
通过绘制不同 5-ALA 类别的免疫浸润图谱，我们为 5-ALA 和神经胶质瘤生物学领域提供了基本的基础见解。在首次组织学数据中，TCGA 数据中的显著相关性并未完全转化为可检测到的免疫浸润差异，这一观察结果值得在更大的队列中进一步研究。
