The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.
The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.
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DOI：
10.1111/imr.12528
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发表时间：
2017-03
影响因子：
8.7
通讯作者：
Stagg J
中科院分区：
文献类型：
--
作者：
Allard B;Longhi MS;Robson SC;Stagg J
癌症能够通过破坏免疫抑制途径来生长，以防止恶性细胞被认为是危险的或外来的。这种机制阻止了癌症被免疫系统消灭，并允许疾病从早期发展到致命状态。免疫疗法是一种新发展的干预手段，通过直接刺激排异反应或阻断抑制途径来改变患者的免疫系统以对抗癌症。胞外腺苷由外核苷酶CD39和CD73产生，是一种新发现的干扰抗肿瘤免疫应答的“免疫检查点介质”。在这篇综述中，我们重点关注CD39和CD73外切酶，包括这些分子的生物化学方面，并详细介绍了它们在免疫细胞上的分布和功能。讨论了CD39和CD73抑制在临床前和临床研究中的作用。最后，我们对腺苷能和其他嘌呤能靶向治疗的潜在临床应用提供了见解，并预测了这些治疗如何与其他抗癌方式联合发展。
Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are newly developing interventions that modify the patient’s immune system to fight cancer, by either directly stimulating rejection-type processes or by blocking suppressive pathways. Extracellular adenosine generated by the ectonucleotidases CD39 and CD73 is a newly recognized “immune checkpoint mediator” that interferes with anti-tumor immune responses. In this review, we focus on CD39 and CD73 ectoenzymes and encompass aspects of the biochemistry of these molecules as well as detailing the distribution and function on immune cells. Effects of CD39 and CD73 inhibition in preclinical and clinical studies are discussed. Finally, we provide insights into potential clinical application of adenosinergic and other purinergic-targeting therapies and forecast how these might develop in combination with other anti-cancer modalities.