【文献解读】腺苷在肿瘤进展中的作用:A2B受体作为潜在的治疗靶点
2017/7/23 创新医学网

    

     文章来源:欧尔意 OAE 微信号 作者:Sofina

    

     原文出处

     Sorrentino C, Morello S. Role of adenosine in tumor progression: focus on A2B receptor as potential therapeutic target. J Cancer Metastasis Treat 2017; 3:127-38.

     DOI:10.20517/2394-4722.2017.29.

     摘要

     腺苷受体是G蛋白偶联受体家族的一种,能在受损组织中调节腺苷的抗炎和免疫抑制作用。大量的证据表明,在缺氧条件下腺苷的积累有利于肿瘤的发展,有助于癌细胞逃避免疫反应。肿瘤细胞和/或淋巴细胞和骨髓细胞可以表达腺苷生成酶CD73和/或A2A受体,其反过来强烈地抑制有效的T细胞介导反应,同时促进抑制细胞的活动,如Treg和骨髓衍生抑制细胞。CD73抑制剂和A2A拮抗剂,无论作为单剂或者结合免疫检查点抑制剂,如抗PD-1单克隆抗体,目前正在癌症患者中进行I期临床试验。最近的研究表明,A2B受体在调节腺苷的促肿瘤效应方面起着重要作用,因为其选择性阻断可以抑制一些鼠肿瘤模型中的肿瘤生长。靶向A2B受体可以减低骨髓细胞诱导的免疫抑制,并抑制肿瘤微环境中基质细胞的活动,从而限制肿瘤血管生成和转移过程。在这里,作者回顾了目前关于A2B受体参与调节肿瘤进展的相关数据,并讨论了A2B受体抑制剂作为癌症治疗中潜在的治疗剂的进展。

     关键词:CD73 / A2腺苷受体轴,A2B腺苷受体,肿瘤免疫,肿瘤转移,肿瘤血管生成,癌症治疗。

     Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue. A large number of evidence indicate that the accumulation of adenosine under hypoxic conditions favors tumor progression, helping cancer cells to evade immune responses. Tumor cells and/or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or A2Areceptor, which in turn strongly suppresses an effective T-cell-mediated response, while promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor cells. CD73 inhibitors and A2A antagonists, either as single agents, or in combination with immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies, are currently in Phase I clinical trial in cancer patients. Recent studies show that A2B receptor plays an important role in mediating the pro-tumor effects of adenosine, since its selective blockade can inhibit tumor growth in some murine tumor models. Targeting A2B receptor reduces immunosuppression induced by myeloid cells and inhibits the stromal cells activity within the tumor microenvironment, limiting tumor angiogenesis and metastatic processes. Here, the authors review the current data on involvement of A2B receptor in regulating tumor progression and discuss the development of A2B receptor inhibitors as potential therapeutic agents in cancer treatment.

     Key words:CD73/A2adenosine receptors axis, A2B adenosine receptor, tumor immunity, tumor metastasis, tumor angiogenesis, cancer treatment.

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