The Tumour Vasculature as a Target to Modulate Leucocyte Trafficking.
The Tumour Vasculature as a Target to Modulate Leucocyte Trafficking.
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DOI：
10.3390/cancers13071724
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发表时间：
2021-04-06
期刊：
影响因子：
5.2
通讯作者：
Gamble J
中科院分区：
文献类型：
--
作者：
Zhao Y;Ting KK;Coleman P;Qi Y;Chen J;Vadas M;Gamble J
肿瘤血管以异常的形态和功能为特征，通过限制适当的白细胞亚群的运输，产生免疫抑制性肿瘤微环境。触发肿瘤血管系统中的表型改变以类似于正常血管系统（称为血管正常化）的策略通过增强白细胞与内皮细胞之间的相互作用促进白细胞有效运输到肿瘤中。这篇综述具体说明了靶向肿瘤血管如何调节白细胞运输的关键步骤。此外，选择性调节白细胞亚群在肿瘤中的运输可以通过血管靶向策略实现，有助于改善免疫治疗，从而延迟肿瘤进展。针对实体瘤的免疫疗法的有效性取决于适当的白细胞亚群在肿瘤微环境（TME）中的运输和积累，其中在内皮处发生募集。这种募集涉及白细胞和血管内皮细胞（EC）之间的相互作用，并通过一系列步骤发生，包括白细胞捕获、滚动、粘附和管腔内爬行，最后是白细胞跨内皮迁移穿过内皮。肿瘤血管系统可以通过影响白细胞募集过程的每一步来抑制白细胞的运输，最终产生免疫抵抗的微环境。通过诸如血管正常化的策略调节肿瘤血管系统已被证明在促进白细胞运输到肿瘤中和增强免疫治疗方面是有效的。在这篇综述中，我们讨论了肿瘤血管异常的潜在机制及其对白细胞运输的影响，以及通过增加白细胞募集来克服肿瘤血管异常以促进免疫治疗的潜在策略。
Tumour blood vessels, characterised by abnormal morphology and function, create an immunosuppressive tumour microenvironment via restricting the appropriate leucocyte subsets trafficking. Strategies to trigger phenotypic alteration in tumour vascular system to resemble normal vascular system, named vascular normalisation, promote effective trafficking of leucocytes into tumours through enhancing the interactions between leucocytes and endothelial cells. This review specifically demonstrates how targeting tumour blood vessels modulates the critical steps of leucocyte trafficking. Furthermore, selective regulation of leucocyte subsets trafficking in tumours can be achieved by vasculature-targeting strategies, contributing to improved immunotherapy and thereby delayed tumour progression. The effectiveness of immunotherapy against solid tumours is dependent on the appropriate leucocyte subsets trafficking and accumulating in the tumour microenvironment (TME) with recruitment occurring at the endothelium. Such recruitment involves interactions between the leucocytes and the endothelial cells (ECs) of the vessel and occurs through a series of steps including leucocyte capture, their rolling, adhesion, and intraluminal crawling, and finally leucocyte transendothelial migration across the endothelium. The tumour vasculature can curb the trafficking of leucocytes through influencing each step of the leucocyte recruitment process, ultimately producing an immunoresistant microenvironment. Modulation of the tumour vasculature by strategies such as vascular normalisation have proven to be efficient in facilitating leucocyte trafficking into tumours and enhancing immunotherapy. In this review, we discuss the underlying mechanisms of abnormal tumour vasculature and its impact on leucocyte trafficking, and potential strategies for overcoming the tumour vascular abnormalities to boost immunotherapy via increasing leucocyte recruitment.
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影响因子：
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