To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.

中文翻译：

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黑色素瘤脑肿瘤的 T 淋巴细胞募集取决于不同的静脉血管


为了改善脑肿瘤的免疫治疗，重要的是要确定从血流中募集 T 细胞的主要颅内部位及其颅内到达脑肿瘤的途径。在颅内黑色素瘤小鼠模型中使用活体显微镜检查，我们发现循环 T 细胞优选粘附和外渗在肿瘤附近的一种独特类型的静脉血管，即瘤周静脉血管 （PVV）。其他血管结构被排除在颅内黑色素瘤的替代 T 细胞途径之外。抗 PD-1/CTLA-4 免疫检查点抑制剂增加了颅内 T 细胞的运动，促进从 PVV 迁移到肿瘤，随后抑制颅内肿瘤生长。内皮粘附分子 ICAM-1 在 PVV 上特别表达，并且在人脑转移样本中，PVV 样血管的 ICAM-1 阳性与瘤内 T 细胞浸润相关。这些发现揭示了免疫系统可以进入和控制脑肿瘤并可能影响其他脑病理的独特机制。