调节性T细胞及CD39^- CD73^-腺苷通路在肿瘤微环境中的研究进展

Research advances on regulatory T cells and CD39^- CD73^- adenosine pathway in tumor microenvironment

调节性T细胞(Treg)是一种重要的CD4+T细胞,在维持体内免疫系统平衡和抵抗外来抗原方面起着重要作用。在肿瘤微环境中,其主要通过细胞间的接触抑制和表面分子及分泌细胞因子等途径发挥免疫抑制作用。近些年研究发现,Treg上一个重要的分子通路:胞外酶CD39-CD73-腺苷通路,通过CD39和CD73的协同作用,ATP被分解产生大量的腺苷,腺苷通过抑制CD4+T、CD8+T和自然杀伤细胞等效应淋巴细胞而发挥着强大的免疫抑制作用,进而促进了肿瘤的发生发展。此外,大量的体内外实验显示,运用单克隆抗体等CD39的抑制剂,特异性阻断CD39的促肿瘤作用,抑制了Treg细胞的抗肿瘤免疫作用,为抗肿瘤免疫治疗提供另一安全有效的途径。本文将就Treg和腺苷通路的发生机制及抗CD39的免疫治疗进行系统综述。

Regulatory T cells （Tregs） are an important subpopulation of CD4＋ T cells, which are essential for maintai- ning the homeostasis of the immune system and excessive immune responses against foreign antigens. In the tumor mi- croenvironment, infiltrated Tregs mediate immunosuppression mainly through multiple surface molecules, cell - contact dependent and independent manner and secretion of cytokines mechanisms. In recent years, a large number of studies have found a new role for the CD39 - CD73 - Adenosine pathway. CD39 ectonucleotidase is the rate - limiting enzyme of a cascade leading to the generation of adenosine that suppresses CD4＋ and CD8 ＋ T cell and also natural killer cell antitumor activities. In addition,the ongoing development of CD39 -blocking monoclonal antibodies are a more safe antitumour drugs. Here,we discuss the mechanisms of Tregs and CD39 - CD73 - Adenosine pathway and review the re- cent literature supporting CD39 as a promising therapeutic target in oncology.