TSPO是脑肿瘤正电子发射计算机体层摄影（PET）成像的一种有前途的新型示踪剂靶点。然而，由于贡献于TSPO-PET信号的细胞种群的异质性，成像的解读可能具有挑战性。因此，我们在胶质瘤中评估了TSPO的富集/表达与其基础组织病理学和分子特征的关联。我们在大型in silico数据集中分析了TSPO表达及其调节机制，并通过对TSPO启动子进行直接亚硫酸盐测序来进行评估。在我们的TSPO-PET成像研究队列的胶质母细胞瘤组织样本中，我们通过免疫组化和荧光多重染色分析了TSPO示踪剂富集和蛋白标记与细胞谱系标记物表达的关联。此外，我们通过RNA测序确定了相关的TSPO相关信号通路。我们发现，TSPO表达与预后不良的胶质瘤表型相关，并且TSPO启动子高甲基化与IDH突变相关。仔细的组织学分析揭示了TSPO免疫组化与TSPO-PET信号的相关性，以及TSPO由多样的细胞种群表达。肿瘤核心区域是整体TSPO信号的主要贡献者，而肿瘤边缘的TSPO信号主要由CD68阳性的小胶质细胞/巨噬细胞驱动。在分子上，高TSPO表达标志着预后不良的胶质母细胞瘤细胞亚群，其特征为富集的间质基因集和更多的肿瘤相关巨噬细胞。总之，我们的研究通过揭示TSPO在胶质瘤中作为成像标记物的IDH依赖性差异、TSPO PET信号的区域异质性以及TSPO在肿瘤免疫细胞相互作用方面的功能影响，进一步提高了对TSPO的认识。© 2023. BioMed Central Ltd.,属于Springer Nature的一部分。

TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing.We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages.In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions.© 2023. BioMed Central Ltd., part of Springer Nature.