文章：

免疫检查点抑制剂介导的心肌炎：心脏中的CTLA4， PD1和LAG3

Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart

原文发布日期：2024-07-09

DOI: 10.1038/s41568-024-00715-5

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

免疫检查点抑制剂（ICIs）已彻底改变肿瘤学领域，近50%的癌症患者符合ICI治疗条件。然而接受ICI治疗的患者面临可能影响任何器官的免疫相关毒性风险。针对细胞毒性T淋巴细胞相关抗原4（CTLA4）、程序性细胞死亡蛋白1（PD1）及其配体PD-L1的ICI所引发的心肌炎症（即心肌炎）虽不常见，但却是潜在致命并发症。随着ICIs的广泛应用、临床识别率的提升以及联合ICI治疗（已明确为ICI心肌炎危险因素）使用的增加，ICI介导的心肌炎（ICI-心肌炎）正逐渐成为重要的临床病症。本文从基础与机制视角切入，整合临床前模型和患者样本的最新数据，提出对免疫检查点分子基础生物学的机制理解或可为疾病进程提供新见解，从而推动诊疗方法的改进。ICI-心肌炎作为新型综合征，我们对于心脏免疫检查点的认知尚处于萌芽阶段，但对其病理生理学的深入探索将有助于完善患者风险分层、优化诊断手段并为患者提供精准化治疗方案。

原文链接：

Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart