Section of Cardio-Oncology & Immunology, Cardiovascular Research Institute (CVRI), University of California San Francisco, School of Medicine, San Francisco, CA, USA.
Yale University School of Medicine, New Haven, CT, USA.
Nat Rev Cancer. 2024 Aug;24(8):540-553. doi: 10.1038/s41568-024-00715-5. Epub 2024 Jul 9.
Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication. ICI-mediated myocarditis (ICI-myocarditis) is a growing clinical entity given the widespread use of ICIs, its increased clinical recognition and growing use of combination ICI treatment, a well-documented risk factor for ICI-myocarditis. In this Review, we approach ICI-myocarditis from a basic and mechanistic perspective, synthesizing the recent data from both preclinical models and patient samples. We posit that mechanistic understanding of the fundamental biology of immune-checkpoint molecules may yield new insights into disease processes, which will enable improvement in diagnostic and therapeutic approaches. The syndrome of ICI-myocarditis is novel, and our understanding of immune checkpoints in the heart is in its nascency. Yet, investigations into the pathophysiology will inform better patient risk stratification, improved diagnostics and precision-based therapies for patients.
免疫检查点抑制剂（ICIs）彻底改变了肿瘤学，几乎所有癌症患者中有近 50%适合用 ICI 治疗。然而，接受 ICI 治疗的患者有发生免疫相关毒性的风险，这种毒性可影响任何器官。ICI 靶向细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）、程序性细胞死亡蛋白 1（PD1）和 PD1 配体 1（PDL1）导致的心肌炎症，即心肌炎，是一种罕见但潜在致命的并发症。鉴于 ICI 的广泛应用、对其认识的提高以及联合 ICI 治疗的应用增加，ICI 介导的心肌炎（ICI 心肌炎）已成为一个日益严重的临床问题。在这篇综述中，我们从基础和机制的角度来探讨 ICI 心肌炎，综合了来自临床前模型和患者样本的最新数据。我们假设对免疫检查点分子的基本生物学的机制理解可能会为疾病进程提供新的见解，从而改进诊断和治疗方法。ICI 心肌炎的综合征是新颖的，我们对心脏中的免疫检查点的理解还处于起步阶段。然而，对病理生理学的研究将为更好地对患者进行风险分层、改进诊断和为患者提供基于精准医学的治疗提供信息。
