Agora癌症研究中心Johanna A. Joyce研究团队取得一项新突破。他们报道了原发性和转移性脑肿瘤内皮细胞和壁细胞的单细胞图谱。该研究于2025年3月18日发表于国际一流学术期刊《免疫学》杂志上。

研究团队综合分析了两种主要的血脑屏障细胞类型，内皮细胞和壁细胞，横跨非肿瘤脑组织，异枸橼酸脱氢酶（IDH）突变体（IDH mut）低级别胶质瘤，IDH野生型（IDH WT）高级别胶质母细胞瘤（GBMs），以及来自各种原发肿瘤的BrMs。整体和单细胞RNA测序，结合空间分析，揭示了GBMs，而不是低级别胶质瘤，在肿瘤血管系统中表现出显著的改变，包括多种病理性血管细胞亚型的出现。

然而，这些改变在GBMs中不如BrMs明显。值得注意的是，BrMs血管系统显示出更高的渗透性和与不同免疫细胞群更广泛的相互作用。该血管图谱提供了对大脑肿瘤特异性血管特征的理解，为开发血管和免疫靶向治疗提供了基础。

据介绍，中枢神经系统（CNS）恶性肿瘤包括原发性肿瘤，如胶质瘤和源自多种颅外肿瘤的脑转移瘤（BrMs）。血脑屏障（BBB）是原发性和转移性脑癌的关键结构组成部分。

附：英文原文

Title: Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors

Author: Leire Bejarano, Joao Lourenco, Annamaria Kauzlaric, Eleni Lamprou, Catia F. Costa, Sabine Galland, Roeltje R. Maas, Paola Guerrero Aruffo, Nadine Fournier, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce

Issue&Volume: 2025-03-18

Abstract: Central nervous system (CNS) malignancies include primary tumors, such as gliomas, and brain metastases (BrMs) originating from diverse extracranial cancers. The blood-brain barrier (BBB) is a key structural component of both primary and metastatic brain cancers. Here, we comprehensively analyzed the two major BBB cell types, endothelial and mural cells, across non-tumor brain tissue, isocitrate dehydrogenase (IDH) mutant (IDH mut) low-grade gliomas, IDH wild-type (IDH WT) high-grade glioblastomas (GBMs), and BrMs from various primary tumors. Bulk and single-cell RNA sequencing, integrated with spatial analyses, revealed that GBMs, but not low-grade gliomas, exhibit significant alterations in the tumor vasculature, including the emergence of diverse pathological vascular cell subtypes. However, these alterations are less pronounced in GBMs than in BrMs. Notably, the BrM vasculature shows higher permeability and more extensive interactions with distinct immune cell populations. This vascular atlas presents a resource toward understanding of tumor-specific vascular features in the brain, providing a foundation for developing vascular- and immune-targeting therapies.

DOI: 10.1016/j.immuni.2025.02.022

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00089-5