van Loon Karlijn, van Breest Smallenburg Mathilda E, Huijbers Elisabeth J M, Griffioen Arjan W, van Beijnum Judy R
Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Angiogenesis Laboratory, Department of Medical Oncology, Amsterdam University Medical Center, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; CimCure BV, Amsterdam, the Netherlands.
Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188985. doi: 10.1016/j.bbcan.2023.188985. Epub 2023 Sep 17.
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.
近年来，人们对在肿瘤微环境中寻找新的抗癌治疗靶点的兴趣迅速增加。更具体地说，肿瘤相关血管是一个很有前景的靶点。我们最近发现，中间丝蛋白波形蛋白在肿瘤脉管系统的内皮细胞中被外化。细胞外波形蛋白通过模拟血管内皮生长因子（VEGF）和支持细胞迁移以及内皮细胞无反应性（内皮细胞对促炎细胞因子无反应）来维持血管生成。后者阻碍免疫细胞浸润，随后使肿瘤逃避免疫。其他研究表明，细胞外波形蛋白在持续的全身和局部炎症中起作用。在这里，我们将回顾细胞外波形蛋白的已报道作用，特别强调其在肿瘤微环境中免疫细胞与内皮细胞相互作用中的参与。为此，我们讨论细胞外波形蛋白调节免疫系统的不同方式。此外，我们回顾这种蛋白质如何通过改变黏附蛋白的表达来改变免疫细胞与血管壁的黏附，减弱免疫细胞浸润到肿瘤实质中。最后，我们讨论靶向波形蛋白的治疗如何能够逆转内皮细胞无反应性并促进免疫浸润，支持抗肿瘤免疫。
