Targeting the CD73-adenosine axis in immuno-oncology
Targeting the CD73-adenosine axis in immuno-oncology
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DOI：
10.1016/j.imlet.2018.05.001
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发表时间：
2019-01-01
影响因子：
4.4
通讯作者：
Stagg, John
中科院分区：
文献类型：
--
作者：
Allard, David;Chrobak, Pavel;Stagg, John
胞外核糖核酸酶CD39和CD73是细胞表面的酶，能将细胞外的ATP分解为腺苷。因此，它们构成了细胞外嘌呤能途径的关键组成部分，在维持组织和免疫平衡方面发挥着重要作用。随着肿瘤免疫治疗时代的到来，胞外核苷酸酶和腺苷受体已成为增强抗肿瘤免疫反应的新的治疗靶点。随着早期临床试验显示出有希望的结果，破译腺苷靶向药物的不同作用机制，识别将从这些药物中受益的患者，并合理开发新的协同组合变得越来越重要。鉴于胞外核苷酸酶和腺苷受体的广泛表达，对细胞特异性作用的更好理解也将是成功实施这一新一代免疫肿瘤疗法的关键。我们在此综述了CD73和腺苷在癌症中作用的最新研究，重点是细胞特异性功能。我们还讨论了正在进行的临床试验和腺苷靶向制剂的未来途径。
The ectonucleotidases CD39 and CD73 are cell surface enzymes that catabolize the breakdown of extracellular ATP into adenosine. As such, they constitute critical components of the extracellular purinergic pathway and play important roles in maintaining tissue and immune homeostasis. With the coming of age of cancer immunotherapy, ectonucleotidases and adenosine receptors have emerged as novel therapeutic targets to enhance antitumor immune responses. With early-phase clinical trials showing promising results, it is becoming increasingly important to decipher the distinct mechanisms-of-action of adenosine-targeting agents, identify patients that will benefit from these agents and rationally develop novel synergistic combinations. Given the broad expression of ectonucleotidases and adenosine receptors, a better understanding of cell-specific roles will also be key for successful implementation of this new generation of immuno-oncology therapeutics. We here review the latest studies on the roles of CD73 and adenosine in cancer with a focus on cell-specific function. We also discuss ongoing clinical trials and future avenues for adenosine-targeting agents.