Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France.
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Br J Pharmacol. 2020 May;177(10):2199-2214. doi: 10.1111/bph.15011. Epub 2020 Mar 12.
Trivalent arsenic (As(III)) is recently found to be an immunomodulatory agent. As(III) has therapeutic potential in several autoimmune and inflammatory diseases in vivo. In vitro, it selectively induces apoptosis of immune cells due to different sensitivity. At a non-toxic level, As(III) shows its multifaceted nature by inducing either pro- or anti-inflammatory functions of immune subsets. These effects are exerted by either As(III)-protein interactions or as a consequence of As(III)-induced homeostasis imbalance. The immunomodulatory properties also show synergistic effects of As(III) with cancer immunotherapy. In this review, we summarize the immunomodulatory effects of As(III), focusing on the effects of As(III) on immune subsets in vitro, on mouse models of immune-related diseases, and the role of As(III) in cancer immunotherapy. Updates of the mechanisms of action, the pioneer clinical trials, dosing, and adverse events of therapeutic As(III) are also provided.
三价砷（As(III)）最近被发现是一种免疫调节剂。As(III)在体内的几种自身免疫性和炎症性疾病中具有治疗潜力。在体外，由于敏感性不同，它选择性地诱导免疫细胞凋亡。在非毒性水平下，As(III)通过诱导免疫亚群的促炎或抗炎功能表现出其多面性。这些作用是通过 As(III-蛋白相互作用或 As(III-诱导的内稳态失衡的结果来发挥的。免疫调节特性还显示出 As(III)与癌症免疫疗法的协同作用。在这篇综述中，我们总结了 As(III)的免疫调节作用，重点介绍了 As(III)对体外免疫亚群、免疫相关疾病小鼠模型的影响，以及 As(III)在癌症免疫疗法中的作用。还提供了作用机制、开创性临床试验、剂量和治疗性 As(III)的不良反应的最新信息。
