Hu Weilei, Wang Guosheng, Wang Yian, Riese Matthew J, You Ming
Center for Disease Prevention Research and Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Department of Biomedical Engineering, Binghamton University-SUNY, 4400 Vestal Pkwy E, Binghamton, NY 13902, USA.
iScience. 2020 Sep 20;23(10):101580. doi: 10.1016/j.isci.2020.101580. eCollection 2020 Oct 23.
Immunotherapy with monoclonal antibodies targeting immune checkpoint molecules, including programmed death-1 (PD-1), PD ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, has become prominent in the treatment of many types of cancer. However, a significant number of patients treated with immune checkpoint inhibitors (ICIs) develop immune-related adverse events (irAEs). irAEs can affect any organ system, and although most are clinically manageable, irAEs can result in mortality or long-term morbidity. Factors that can predict irAEs remain elusive. Understanding the etiology of ICI-induced irAEs and ways to limit these adverse events are needed. In this review, we provide basic science and clinical insights on the mechanisms responsible for ICI efficacy and ICI-induced irAEs. We further provide insights into approaches that may uncouple irAEs from the ability of ICIs to kill tumor cells.
使用靶向免疫检查点分子的单克隆抗体进行免疫治疗，包括程序性死亡-1（PD-1）、PD配体-1（PD-L1）和细胞毒性T淋巴细胞相关抗原（CTLA）-4，在多种癌症的治疗中已变得突出。然而，大量接受免疫检查点抑制剂（ICI）治疗的患者会出现免疫相关不良事件（irAE）。irAE可影响任何器官系统，尽管大多数在临床上可控制，但irAE可导致死亡或长期发病。能够预测irAE的因素仍然难以捉摸。需要了解ICI诱导的irAE的病因以及限制这些不良事件的方法。在本综述中，我们提供了关于ICI疗效和ICI诱导的irAE的机制的基础科学和临床见解。我们还进一步探讨了可能使irAE与ICI杀死肿瘤细胞的能力脱钩的方法。
