Targeting the tumor vasculature to enhance T cell activity.
Targeting the tumor vasculature to enhance T cell activity.
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DOI：
10.1016/j.coi.2015.01.011
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发表时间：
2015-04
影响因子：
7
通讯作者：
Coukos G
中科院分区：
文献类型：
--
作者：
Lanitis E;Irving M;Coukos G
肿瘤血管形成阻碍肿瘤内T细胞运输的物理屏障。肿瘤内皮细胞可直接杀伤T细胞或抑制其活性。肿瘤内皮屏障的正常化增强了T细胞的浸润和活性。肿瘤血管靶向与主动和过继免疫疗法协同作用。广泛的小鼠肿瘤模型研究证明，T细胞在肿瘤免疫监测中发挥着关键作用，并鼓励患者对过继性T细胞疗法和树突状细胞疫苗产生反应。肿瘤细胞与其局部细胞环境的相互作用可以触发免疫抑制T细胞的事件。最近，人们发现肿瘤血管本身是T细胞的重要屏障。血管内的内皮细胞可以抑制T细胞的活性，以破坏T细胞为目标，并通过解除粘附分子的管制，首先阻止T细胞进入肿瘤。在这里，我们回顾了打破肿瘤内皮屏障和增强T细胞活性的方法。
Tumor vessels form a physical barrier that hampers intratumoral T cell trafficking. Tumor endothelial cells can directly kill T cells or suppress their activity. Normalization of the tumor endothelial barrier enhances T cell infiltration and activity. Tumor vascular targeting synergizes with active and adoptive immunotherapies. T cells play a critical role in tumor immune surveillance as evidenced by extensive mouse-tumor model studies as well as encouraging patient responses to adoptive T cell therapies and dendritic cell vaccines. It is well established that the interplay of tumor cells with their local cellular environment can trigger events that are immunoinhibitory to T cells. More recently it is emerging that the tumor vasculature itself constitutes an important barrier to T cells. Endothelial cells lining the vessels can suppress T cell activity, target them for destruction, and block them from gaining entry into the tumor in the first place through the deregulation of adhesion molecules. Here we review approaches to break this tumor endothelial barrier and enhance T cell activity.