Vergara Andrea, De Felice Marco, Cesaro Arturo, Gragnano Felice, Pariggiano Ivana, Golia Enrica, De Pasquale Antonio, Blasi Ettore, Fimiani Fabio, Monda Emanuele, Limongelli Giuseppe, Calabrò Paolo
Department of Translational Medical Sciences, University of Campania 'Luigi Vanvitelli', Caserta, Italy.
Division of Clinical Cardiology, A.O.R.N. 'Sant'Anna e San Sebastiano', Caserta, Italy.
Angiology. 2024 Nov-Dec;75(10):909-920. doi: 10.1177/00033197231201929. Epub 2023 Sep 12.
Immune checkpoint inhibitors (ICIs) are specific monoclonal antibodies directed against inhibitory targets of the immune system, mainly represented by programmed death-1 (PD1) ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), thus enabling an amplified T-cell-mediated immune response against cancer cells. These drugs have significantly improved prognosis in patients with advanced metastatic cancer (e.g., melanoma, non-small cell lung cancer, renal cell carcinoma). However, uncontrolled activation of anti-tumor T-cells could trigger an excessive immune response, possibly responsible for multi-organ damage, including, among others, lymphocytic myocarditis. The incidence of ICIs-induced myocarditis is underestimated and the patients affected are poorly characterized. The diagnosis and management of this condition are mainly based on expert opinion and case reports. EKG and ultrasound are tests that can help identify patients at risk of myocarditis during treatment by red flags, such as QRS complex enlargement and narrowing of global longitudinal strain (GLS). Therapy of ICI-related myocarditis is based on immunosuppressors, monoclonal antibodies and fusion proteins. A future strategy could involve the use of microRNAs. This review considers the current state of the art of immune-related adverse cardiovascular events, focusing on histological and clinical features, diagnosis and management, including current treatments and future pharmacological targets.
免疫检查点抑制剂（ICIs）是一类特异性单克隆抗体，主要针对免疫系统的抑制性靶点，以程序性死亡蛋白1（PD1）及其配体1（PD-L1）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）为代表，从而增强T细胞介导的针对癌细胞的免疫反应。这些药物显著改善了晚期转移性癌症（如黑色素瘤、非小细胞肺癌、肾细胞癌）患者的预后。然而，抗肿瘤T细胞的失控激活可能引发过度免疫反应，这可能是多器官损伤的原因，其中包括淋巴细胞性心肌炎。ICIs诱导的心肌炎发病率被低估，且受影响患者的特征描述不足。这种疾病的诊断和管理主要基于专家意见和病例报告。心电图（EKG）和超声检查有助于通过QRS波群增宽和整体纵向应变（GLS）变窄等警示信号识别治疗期间有心肌炎风险的患者。ICI相关心肌炎的治疗基于免疫抑制剂、单克隆抗体和融合蛋白。未来的策略可能涉及使用微小RNA。本综述探讨了免疫相关不良心血管事件的当前研究现状，重点关注组织学和临床特征、诊断和管理，包括当前治疗方法和未来的药理学靶点。
