Baris Adrian M, Fraile-Bethencourt Eugenia, Anand Sudarshan
Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Cancers (Basel). 2021 Sep 3;13(17):4452. doi: 10.3390/cancers13174452.
Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors, such as cGAS-STING, in combination with immunotherapies. In this review, we present a case for targeting nucleic acid-sensing pathways within the tumor vasculature to invigorate tumor-immune responses. We introduce two specific nucleic acid sensors-the DNA sensor TREX1 and the RNA sensor RIG-I-and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid-sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment by co-opting both vascular and immune cell types.
内皮细胞在组织和免疫细胞之间形成了一个强大的界面。事实上，内皮细胞一个未得到充分重视的作用是协调对特定部位的免疫关注。肿瘤内皮细胞具有独特的抑制免疫反应的能力，从而维持免疫抑制微环境。最近在癌症中触发免疫反应的方法集中在激活核酸传感器，如cGAS-STING，并结合免疫疗法。在这篇综述中，我们提出了一个针对肿瘤脉管系统内核酸感应通路来增强肿瘤免疫反应的案例。我们介绍了两种特定的核酸传感器——DNA传感器TREX1和RNA传感器RIG-I，并讨论它们在脉管系统中的功能作用。最后，我们阐述了在抗血管生成和免疫激活背景下如何靶向肿瘤内皮中的这些核酸传感器。我们相信，了解核酸感应在肿瘤脉管系统中的作用可以增强我们通过协同血管和免疫细胞类型来设计更有效的靶向肿瘤微环境疗法的能力。
