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CD73 作为癌症免疫治疗的潜在机会。

CD73 as a potential opportunity for cancer immunotherapy.

机构信息

a Cellular and Molecular Research Center , Yasuj University of Medical Sciences , Yasuj , Iran.

b Department of Immunology, School of Medicine , Iran University of Medical Sciences , Tehran , Iran.

出版信息

Expert Opin Ther Targets. 2019 Feb;23(2):127-142. doi: 10.1080/14728222.2019.1559829. Epub 2018 Dec 26.

Abstract

Cancer cells apply various mechanisms to induce and enhance immune escape. The complex network of immune-response modulating factors in the tumor microenvironment is a reason for the difficulties encountered when attempting to treat many cancers. Adenosine is a potent immune-modulating factor that can be generated through the degradation of ATP by cooperative action of NTPDase1 (CD39) and ecto-5'-nucleotidase (CD73) molecules. Overexpression of CD73 on tumor and immune cells leads to the presence of a high concentration of this factor in the tumor region. Upregulation of CD73 is associated with the overproduction of adenosine; it suppresses antitumor immune responses and helps proliferation, angiogenesis, and metastasis. Areas covered: We attempt to clarify the immunobiology of CD73 in association with its role in cancer development, angiogenesis, and metastasis. Moreover, we have reviewed CD73-targeting studies and highlighted CD73 as a potent target for cancer immunotherapy. Expert opinion: It seems that blockade of CD73, in combination with immune checkpoint inhibitors such as anti-PD-L1 and anti-CTLA-4, can be a novel promising therapeutic strategy that can be evaluated in the future trials.

摘要

癌细胞应用各种机制来诱导和增强免疫逃逸。肿瘤微环境中免疫反应调节因子的复杂网络是许多癌症治疗困难的原因。腺苷是一种有效的免疫调节因子,可以通过 NTPDase1(CD39)和外核苷酸酶(CD73)分子的协同作用降解 ATP 产生。肿瘤细胞和免疫细胞上 CD73 的过度表达导致肿瘤区域存在高浓度的这种因子。CD73 的上调与腺苷的过度产生有关;它抑制抗肿瘤免疫反应,有助于增殖、血管生成和转移。涵盖领域:我们试图阐明 CD73 的免疫生物学及其在癌症发展、血管生成和转移中的作用。此外,我们还回顾了 CD73 靶向研究,并强调 CD73 是癌症免疫治疗的一个有效靶点。专家意见:似乎阻断 CD73,结合免疫检查点抑制剂,如抗 PD-L1 和抗 CTLA-4,可以是一种新的有前途的治疗策略,可以在未来的试验中进行评估。

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