Mauge Laetitia, Terme Magali, Tartour Eric, Helley Dominique
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France ; Service d'Hématologie Biologique, Hôpital Européen Georges Pompidou , Paris , France.
INSERM U970, PARCC (Paris Cardiovascular Research Center), Université Paris-Descartes, Sorbonne Paris Cité , Paris , France.
Front Oncol. 2014 Mar 28;4:61. doi: 10.3389/fonc.2014.00061. eCollection 2014.
vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by an abnormal vessel structure and permeability, and by a specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intra-tumoral immune responses and contribute to the development of intra-tumoral immunosuppression, which is a major mechanism for promoting the development, progression, and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of anti-tumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.
如今，内皮被描述为一个调节各种过程的完整器官：血管张力、凝血、炎症和免疫细胞运输，这取决于血管部位及其特定的微环境，以及内皮细胞内在机制，如表观遗传变化。在本综述中，我们将重点关注肿瘤血管系统对适应性免疫反应的控制。在生理条件下，内皮作为一种屏障，通过特定表达粘附分子来调节细胞运输，使免疫细胞能够粘附在血管上，随后渗出。这个过程还取决于趋化因子和整合素的表达，以及决定内皮通透性的连接类型。内皮细胞还可以调节免疫细胞的激活。事实上，由于内皮与免疫细胞的密切相互作用以及共刺激或共抑制信号的传递，内皮层可以构成免疫突触。在肿瘤状态下，血管系统的特征是血管结构和通透性异常，以及内皮细胞的特定表型。所有这些异常都会导致肿瘤内免疫反应的调节，并促进肿瘤内免疫抑制的发展，这是促进肿瘤发生、发展和治疗耐药性的主要机制。对这些各种异常的深入分析将有助于确定抗肿瘤治疗发展的新靶点。此外，血浆生物标志物所识别的内皮细胞表型的最终变化可以作为监测治疗效果的次要指标。
