研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

T 淋巴细胞向黑色素瘤脑肿瘤的募集取决于不同的静脉血管。

T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels.

发表日期:2024 Sep 28
作者: Julia M Messmer, Calvin Thommek, Manuel Piechutta, Varun Venkataramani, Rebekka Wehner, Dana Westphal, Marc Schubert, Chanté D Mayer, Maike Effern, Anna S Berghoff, Daniel Hinze, Iris Helfrich, Dirk Schadendorf, Wolfgang Wick, Michael Hölzel, Matthia A Karreman, Frank Winkler
来源: IMMUNITY

摘要:

为了改善脑肿瘤的免疫治疗,确定 T 细胞从血流中募集的主要颅内部位及其颅内到达脑肿瘤的途径非常重要。在颅内黑色素瘤小鼠模型中使用活体显微镜,我们发现循环 T 细胞更容易粘附并外渗到肿瘤附近的一种不同类型的静脉血管,即肿瘤周围静脉血管 (PVV)。其他血管结构被排除作为颅内黑色素瘤的替代 T 细胞途径。抗 PD-1/CTLA-4 免疫检查点抑制剂可增加颅内 T 细胞运动,促进从 PVV 迁移到肿瘤,从而抑制颅内肿瘤生长。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访问和控制脑肿瘤并可能影响其他脑部病理的独特机制。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
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.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.