CD73 is an important ectoenzyme responsible for the production of extracellular adenosine. It is involved in regulating inflammatory responses and cell migration and is overexpressed in various cancers. The functions of CD73 in blood endothelial cells are understood in detail, but its role on afferent lymphatics remains unknown. Moreover, anti‐CD73 antibodies are now used in multiple clinical cancer trials, but their effects on different endothelial cell types have not been studied. This study reveals that a previously unknown role of CD73 on afferent lymphatics is to dampen immune responses. Knocking it out or suppressing it by siRNA leads to the upregulation of inflammation‐associated genes on lymphatic endothelial cells and a more pro‐inflammatory phenotype of interacting dendritic cells in vitro and in vivo. In striking contrast, anti‐CD73 antibodies had only negligible effects on the gene expression of lymphatic‐ and blood‐endothelial cells. Our data thus reveal new functions of lymphatic CD73 and indicate a low likelihood of endothelial cell–related adverse effects by CD73 targeting therapeutic antibodies.

中文翻译：

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CD73 有助于人类和小鼠传入淋巴内皮细胞的抗炎特性。

CD73是一种重要的胞外酶，负责产生细胞外腺苷。它参与调节炎症反应和细胞迁移，并在各种癌症中过度表达。CD73 在血液内皮细胞中的功能已被详细了解，但其对传入淋巴管的作用仍不清楚。此外，抗CD73抗体现已用于多项临床癌症试验，但其对不同内皮细胞类型的影响尚未研究。这项研究揭示了 CD73 对传入淋巴管的一个先前未知的作用是抑制免疫反应。通过 siRNA 敲除或抑制它，会导致淋巴内皮细胞上炎症相关基因的上调，以及体外和体内相互作用的树突状细胞的促炎表型。与此形成鲜明对比的是，抗 CD73 抗体对淋巴和血液内皮细胞的基因表达的影响可以忽略不计。因此，我们的数据揭示了淋巴 CD73 的新功能，并表明 CD73 靶向治疗抗体产生内皮细胞相关副作用的可能性较低。