Institute of Cancer Research and Comprehensive Cancer Center, Department of Medicine I , Medical University of Vienna , Borschkegasse 8a , A-1090 Vienna , Austria.
Research Cluster "Translational Cancer Therapy Research" , University of Vienna and Medical University of Vienna , Vienna , Austria.
Chem Rev. 2019 Jan 23;119(2):1519-1624. doi: 10.1021/acs.chemrev.8b00396. Epub 2018 Nov 29.
The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.
免疫系统不仅部署了多种先天和适应性机制来抵御病原体，还能预防恶性转化（“免疫监视”）。因此，临床上明显的肿瘤已经反映了那些能够逃避免疫识别的恶性细胞克隆的选择（“免疫逃逸”）。除了其广泛研究的细胞毒性抗癌作用外，金属药物还大量与癌症-免疫界面相互作用，并能逆转免疫逃逸的重要方面。基于与抗癌免疫疗法（例如免疫检查点抑制剂）的联合方法，这一策略最近在临床环境中取得了令人兴奋的初步成果，最近引起了人们的极大关注。这篇综述总结了关于金属药物与抗癌免疫反应的保真度相互作用的有希望但仍然非常零碎的知识，以及它们在不良反应中的作用。它强调了，至少在某些情况下，金属药物可以诱导持久的抗癌免疫反应。这个过程中的重要步骤包括改变癌细胞对先天和适应性免疫的可见性和易感性，以及对免疫细胞群体和肿瘤微环境的直接影响。在此基础上，我们建议启动联合多学科项目，将全面的免疫分析纳入开发新型智能抗癌金属化合物的策略中。
