Department of Medicine, Stanford University, Stanford, California 94305, USA; Stanford Cardiovascular Institute, Stanford University, Stanford, California 94305, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Department of Medicine, Stanford University, Stanford, California 94305, USA.
J Mol Cell Cardiol. 2021 Nov;160:121-127. doi: 10.1016/j.yjmcc.2021.07.006. Epub 2021 Jul 22.
Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy, but their use carries a high risk of cardiac immune related adverse events (iRAEs). With the expanding utilization of ICI therapy, there is a growing need to understand the underlying mechanisms behind their anti-tumor activity as well as their immune-mediated toxicities. In this review, we will focus on clinical characteristics and immune pathways of ICI cardiotoxicity, with an emphasis on single-cell technologies used to gain insights in this field. We will focus on three key areas of ICI-mediated immune pathways, including the anti-tumor immune response, the augmentation of the immune response by ICIs, and the pathologic "autoimmune" response in some individuals leading to immune-mediated toxicity, as well as local factors in the myocardial immune environment predisposing to autoimmunity. Discerning the underlying mechanisms of these immune pathways is necessary to inform the development of targeted therapies for ICI cardiotoxicities and reduce treatment related morbidity and mortality.
免疫检查点抑制剂 (ICI) 改变了癌症治疗的格局,但它们的使用存在很高的心脏免疫相关不良事件 (iRAE) 风险。随着 ICI 治疗的广泛应用,越来越需要了解其抗肿瘤活性及其免疫介导毒性的潜在机制。在这篇综述中,我们将重点关注 ICI 心脏毒性的临床特征和免疫途径,重点介绍用于深入了解这一领域的单细胞技术。我们将重点关注三个关键领域的 ICI 介导的免疫途径,包括抗肿瘤免疫反应、ICI 增强免疫反应以及某些个体中导致免疫介导毒性的病理性“自身免疫”反应,以及心肌免疫环境中的局部因素导致自身免疫倾向。辨别这些免疫途径的潜在机制对于为 ICI 心脏毒性开发靶向治疗并降低治疗相关发病率和死亡率是必要的。