Understanding high endothelial venules: Lessons for cancer immunology.
Understanding high endothelial venules: Lessons for cancer immunology.
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DOI：
10.1080/2162402x.2015.1008791
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发表时间：
2015-06
期刊：
影响因子：
7.2
通讯作者：
May MJ
中科院分区：
文献类型：
--
作者：
Ager A;May MJ
高内皮微静脉（HEVs）是特别适于淋巴细胞运输的血管，其通常存在于次级淋巴器官如淋巴结（LN）和派尔集合淋巴结（Peyer’s patch）中。长期以来，人们已经知道HEV在由自身免疫、感染或同种异体移植物驱动的慢性炎症期间在非淋巴器官中发展。最近，已经在实体血管化肿瘤中观察到HEV，并且它们的存在与减小的肿瘤尺寸和改善的患者结果相关。有人提出，新形成的戊型肝炎病毒促进抗肿瘤免疫招募幼稚淋巴细胞进入肿瘤，从而允许局部产生癌组织破坏淋巴细胞。因此，了解HEV如何发展和发挥作用对于揭示它们在人类癌症中的作用非常重要。在LN中，HEV在胚胎和出生后早期发育，并由LN微环境积极维持。全身阻断光敏素-β受体可导致HEV去分化，但诱导HEV分化的LN组分仍不清楚。最近使用基因靶向小鼠的优雅研究清楚地表明，触发内皮细胞（EC）中的光敏素-β受体诱导HEV分化，并且CD11c+树突状细胞在此过程中起关键作用。重要的是要确定EC中的光敏素-β受体依赖性信号传导是否在肿瘤发生期间驱动HEV的发展，以及哪些细胞具有HEV诱导剂特性。这可能揭示促进HEV新生的治疗方法，并确定新形成的HEV对肿瘤免疫的影响。
High endothelial venules (HEVs) are blood vessels especially adapted for lymphocyte trafficking which are normally found in secondary lymphoid organs such as lymph nodes (LN) and Peyer's patches. It has long been known that HEVs develop in non-lymphoid organs during chronic inflammation driven by autoimmunity, infection or allografts. More recently, HEVs have been observed in solid, vascularized tumors and their presence correlated with reduced tumor size and improved patient outcome. It is proposed that newly formed HEV promote antitumor immunity by recruiting naive lymphocytes into the tumor, thus allowing the local generation of cancerous tissue-destroying lymphocytes. Understanding how HEVs develop and function are therefore important to unravel their role in human cancers. In LN, HEVs develop during embryonic and early post-natal life and are actively maintained by the LN microenvironment. Systemic blockade of lymphotoxin-β receptor leads to HEV de-differentiation, but the LN components that induce HEV differentiation have remained elusive. Recent elegant studies using gene-targeted mice have demonstrated clearly that triggering the lymphotoxin-β receptor in endothelial cells (EC) induces the differentiation of HEV and that CD11c+ dendritic cells play a crucial role in this process. It will be important to determine whether lymphotoxin-β receptor-dependent signaling in EC drives the development of HEV during tumorigenesis and which cells have HEV-inducer properties. This may reveal therapeutic approaches to promote HEV neogenesis and determine the impact of newly formed HEV on tumor immunity.