Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity.
Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity.
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癌症免疫检查点阻断疗法及其相关的自身免疫心脏毒性。
DOI：
10.1038/s41401-018-0062-2
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发表时间：
2018
影响因子：
8.2
通讯作者：
Zhu,Hua
中科院分区：
文献类型：
--
作者：
Zhang,Jiu-Cheng;Chen,Wei-Dong;Alvarez,JeanBustamante;Jia,Kelly;Shi,Lei;Wang,Qiang;Zou,Ning;He,Kai;Zhu,Hua
免疫检查点分子是在进化过程中出现的，旨在保护宿主免受激活的T细胞的自我攻击。然而，作为生存和扩张的策略，癌细胞可以劫持这些分子和机制来抑制 T 细胞介导的免疫反应。因此，在发现抑制性T细胞共同受体细胞毒性T淋巴细胞相关蛋白4（CTLA-4）后，通过阻断检查点分子来增强宿主免疫系统的抗肿瘤活性，并进一步增强对PD-1及其配体的识别，人们提出了一种阻断检查点分子以增强宿主免疫系统抗肿瘤活性的思路，并将其应用于癌症治疗。自 2010 年以来，多种检查点抑制剂已获得 FDA 批准，还有更多药物正在进行临床试验。在晚期癌症的治疗中，这些抑制剂显着提高了缓解率和生存获益。然而，伴随着惊人的结果，观察和报告了许多器官中广泛发生的免疫相关不良事件（irAE），其中一些是致命的。在此，我们首先回顾了免疫检查点分子的研究进展及其阻断抗体在癌症治疗中的应用，然后讨论了治疗引起的心脏毒性以及该不良事件发生时的监测和处理策略。
The immune checkpoint molecules are emerged in the evolution to protect the host from self-attacks by activated T cells. However, cancer cells, as a strategy to survive and expand, can hijack these molecules and mechanisms to suppress T cell-mediated immune responses. Therefore, an idea of blocking the checkpoint molecules to enhance the anti-tumor activities of the host immune system has been developed and applied to the cancer therapy after discovery of the inhibitory T cell co-receptor, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and further enhanced on the identification of PD-1 and its ligands. Since 2010, several checkpoint inhibitors have been approved by FDA and many more are in clinical trials. In the treatment of advanced cancers, these inhibitors significantly increased response rates and survival benefits. However, accompanied with the striking results, immune-related adverse events (irAEs) that broadly occurred in many organs were observed and reported, some of which were fatal. Herein, we first review the recent progressions in the research of the immune checkpoint molecules and the application of their blocking antibodies in cancer treatment, and then discuss the cardiac toxicity induced by the therapy and the strategy to monitor, manage this adverse event when it occurs.