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Targeting CD39 in cancer.
Nature Reviews Immunology ( IF 100.3 ) Pub Date : 2020-07-29 , DOI: 10.1038/s41577-020-0376-4
Achim K Moesta 1 , Xian-Yang Li 2 , Mark J Smyth 2
Affiliation  

The ATP–adenosine pathway functions as a key modulator of innate and adaptive immunity within the tumour microenvironment. Consequently, multiple clinical strategies are being explored to target this pathway for the treatment of cancer; in particular, recent clinical data with CD73 antagonists and inhibitors of A2A receptors have demonstrated the therapeutic potential of modulating this pathway. Now, inhibitors of the ectonucleotidase CD39, the rate-limiting enzyme in the conversion of ATP to immunomodulatory adenosine, are entering clinical trials. Consequently, there is currently a focus on understanding the impact of CD39 enzymatic function on innate and adaptive immunity and how therapeutic modulation of this pathway alters their functional potential within the tumour microenvironment. Recent findings reveal multipronged mechanisms of action of CD39 antagonism that rely not only on preventing the accumulation of adenosine but also on the stabilization of pro-inflammatory extracellular ATP to restore antitumour immunity. Here, we review the impact of CD39 expression and ectonucleotidase activity on immunity with a focus on the setting of oncology. Additionally, we discuss the implications for immunotherapy strategies targeting CD39, including their inclusion in rational combination therapies.



中文翻译:

针对CD39的癌症。

ATP-腺苷途径是肿瘤微环境中先天性和适应性免疫的关键调节剂。因此,正在探索多种临床策略来靶向这种治疗癌症的途径。特别是CD73拮抗剂和A 2A抑制剂的最新临床数据受体已证明调节该途径的治疗潜力。现在,胞外核苷酸酶CD39(一种将ATP转换为免疫调节腺苷的速率限制酶)的抑制剂正在进入临床试验。因此,目前的重点是了解CD39酶功能对先天性和适应性免疫的影响,以及该途径的治疗性调节如何改变其在肿瘤微环境中的功能潜能。最近的发现揭示了CD39拮抗作用的多方面作用机制,其不仅依赖于防止腺苷的积累,而且依赖于促炎性细胞外ATP的稳定以恢复抗肿瘤免疫力。在这里,我们回顾了CD39表达和外切核苷酸酶活性对免疫的影响,重点是肿瘤学的设置。

更新日期:2020-07-29
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