Bejarano Leire, Lourenco Joao, Kauzlaric Annamaria, Lamprou Eleni, Costa Catia F, Galland Sabine, Maas Roeltje R, Guerrero Aruffo Paola, Fournier Nadine, Brouland Jean-Philippe, Hottinger Andreas F, Daniel Roy T, Hegi Monika E, Joyce Johanna A
Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland; Agora Cancer Research Centre, Lausanne, Switzerland; Lundin Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Agora Cancer Research Centre, Lausanne, Switzerland; Translational Data Science Facility, Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Immunity. 2025 Apr 8;58(4):1015-1032.e6. doi: 10.1016/j.immuni.2025.02.022. Epub 2025 Mar 18.
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.
中枢神经系统（CNS）恶性肿瘤包括原发性肿瘤，如胶质瘤，以及源自各种颅外癌症的脑转移瘤（BrM）。血脑屏障（BBB）是原发性和转移性脑癌的关键结构组成部分。在这里，我们全面分析了两种主要的血脑屏障细胞类型，即内皮细胞和平滑肌细胞，涵盖非肿瘤脑组织、异柠檬酸脱氢酶（IDH）突变型（IDH mut）低级别胶质瘤、IDH野生型（IDH WT）高级别胶质母细胞瘤（GBM）以及来自各种原发性肿瘤的脑转移瘤。大量和单细胞RNA测序，结合空间分析，揭示了胶质母细胞瘤而非低级别胶质瘤在肿瘤脉管系统中表现出显著改变，包括出现多种病理性血管细胞亚型。然而，这些改变在胶质母细胞瘤中不如在脑转移瘤中明显。值得注意的是，脑转移瘤脉管系统表现出更高的通透性以及与不同免疫细胞群体更广泛的相互作用。这个血管图谱为理解脑中肿瘤特异性血管特征提供了资源，为开发针对血管和免疫的治疗方法奠定了基础。
