多年来，在肿瘤微环境中寻找抗癌治疗的新靶点的兴趣迅速增加。更具体地说，与肿瘤相关的血管是一个有希望的靶点。我们最近发现，中间丝蛋白蛋白质维门蛋白（vimentin）被肿瘤血管内皮细胞外化。已经显示细胞外维门蛋白通过模仿血管内皮生长因子（VEGF），支持细胞迁移以及内皮细胞失活，即内皮对促炎细胞因子的非响应性来维持新生血管形成。后者阻碍了免疫细胞浸润并随之产生逃避肿瘤免疫的效果。其他研究表明细胞外维门蛋白在持续的系统和局部炎症中起了作用。在本文中，我们将回顾有关细胞外维门蛋白的已报告角色，重点关注其在免疫细胞与肿瘤微环境内血管内皮之间相互作用中的参与情况。为此，我们将讨论细胞外维门蛋白通过不同方式调节免疫系统的方式。此外，我们将回顾该蛋白如何通过改变粘附蛋白的表达，影响免疫细胞和血管壁的粘附，从而减轻免疫细胞进入肿瘤实质的情况。最后，我们讨论如何通过针对维门蛋白的治疗来逆转内皮细胞失活，促进免疫浸润，从而支持抗肿瘤免疫。©2023作者发表，版权归Elsevier B.V.所有。保留所有权利。

The interest in finding new targets in the tumor microenvironment for anti-cancer therapy has increased rapidly over the years. More specifically, the tumor-associated blood vessels are a promising target. We recently found that the intermediate filament protein vimentin is externalized by endothelial cells of the tumor vasculature. Extracellular vimentin was shown to sustain angiogenesis by mimicking VEGF and supporting cell migration, as well as endothelial cell anergy, the unresponsiveness of the endothelium to proinflammatory cytokines. The latter hampers immune cell infiltration and subsequently provides escape from tumor immunity. Other studies showed that extracellular vimentin plays a role in sustained systemic and local inflammation. Here we will review the reported roles of extracellular vimentin with a particular emphasis on its involvement in the interactions between immune cells and the endothelium in the tumor microenvironment. To this end, we discuss the different ways by which extracellular vimentin modulates the immune system. Moreover, we review how this protein can alter immune cell-vessel wall adhesion by altering the expression of adhesion proteins, attenuating immune cell infiltration into the tumor parenchyma. Finally, we discuss how vimentin-targeting therapy can reverse endothelial cell anergy and promote immune infiltration, supporting anti-tumor immunity.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.