文章：

肿瘤微环境中的细胞外ATP和P2嘌呤能信号

Extracellular ATP and P2 purinergic signalling in the tumour microenvironment

原文发布日期：2018-07-13

DOI: 10.1038/s41568-018-0037-0

类型: Review Article

开放获取: 否

英文摘要：

Modulation of the biochemical composition of the tumour microenvironment is a new frontier of cancer therapy. Several immunosuppressive mechanisms operate in the milieu of most tumours, a condition that makes antitumour immunity ineffective. One of the most potent immunosuppressive factors is adenosine, which is generated in the tumour microenvironment owing to degradation of extracellular ATP. Accruing evidence over the past few years shows that ATP is one of the major biochemical constituents of the tumour microenvironment, where it acts at P2 purinergic receptors expressed on both tumour and host cells. Stimulation of P2 receptors has different effects depending on the extracellular ATP concentration, the P2 receptor subtype engaged and the target cell type. Among P2 receptors, the P2X purinergic receptor 7 (P2X7R) subtype appears to be a main player in host–tumour cell interactions. Preclinical studies in several tumour models have shown that P2X7R targeting is potentially a very effective anticancer treatment, and many pharmaceutical companies have now developed potent and selective small molecule inhibitors of P2X7R. In this Review, we report on the multiple mechanisms by which extracellular ATP shapes the tumour microenvironment and how its stimulation of host and tumour cell P2 receptors contributes to determining tumour fate.

摘要翻译： 

调节肿瘤微环境的生化组成是癌症治疗的新前沿。大多数肿瘤微环境中存在多种免疫抑制机制，导致抗肿瘤免疫失效。腺苷是最有效的免疫抑制因子之一，由细胞外ATP在肿瘤微环境中降解产生。过去数年的证据表明，ATP是肿瘤微环境的主要生化成分之一，通过表达在肿瘤细胞和宿主细胞上的P2嘌呤能受体发挥作用。P2受体的刺激效应取决于细胞外ATP浓度、激活的P2受体亚型以及靶细胞类型。在P2受体中，P2X7R亚型似乎是宿主-肿瘤细胞相互作用的关键角色。多项肿瘤模型的临床前研究表明，靶向P2X7R可能成为非常有效的抗癌疗法，目前多家制药公司已开发出强效选择性P2X7R小分子抑制剂。本综述将阐述细胞外ATP塑造肿瘤微环境的多重机制，以及其对宿主和肿瘤细胞P2受体的刺激如何影响肿瘤命运。

原文链接：

Extracellular ATP and P2 purinergic signalling in the tumour microenvironment