Department of Translational Medical Sciences (DISMET), Center for Basic and Clinical Immunology Research (CISI), Interdepartmental Center of Clinical and Translational Sciences (CIRCET), Interdepartmental Hypertension Research Center (CIRIAPA), Federico II University, Naples, Italy.
Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Eur J Heart Fail. 2024 Oct;26(10):2055-2076. doi: 10.1002/ejhf.3340. Epub 2024 Aug 1.
The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.
免疫疗法的出现彻底改变了过去十年中实体瘤和血液系统恶性肿瘤的治疗方法。激活免疫系统靶向癌细胞的已批准疗法可大致分为两类。第一类是抑制免疫检查点信号的抗体，称为免疫检查点抑制剂（ICI）。第二类是基于细胞的免疫疗法，包括嵌合抗原受体 T 淋巴细胞（CAR-T）细胞疗法、自然杀伤（NK）细胞疗法和肿瘤浸润淋巴细胞（TIL）疗法。所有这些治疗方法的临床疗效通常都超过了风险，但免疫相关不良事件（irAE）的发生率很高，其发生时间往往不可预测，临床后果从轻（如皮疹）到重甚至致命（如心肌炎、细胞因子释放综合征）不等，且可从可逆转为永久性（如内分泌疾病）。irAE 病理的机制因不同的 irAE 并发症和综合征而异，反映了观察到的广泛临床表型和不同个体免疫反应的可变性，总体而言，其机制仍未完全了解。免疫相关心血管毒性已经出现，我们的认识也从最初集中于罕见但致命的 ICI 相关性心肌炎合并心源性休克发展到更常见的并发症，包括不太严重的 ICI 相关性心肌炎、心包炎、心律失常，包括传导系统疾病和心脏传导阻滞、非炎症性心力衰竭、心尖球形综合征和冠状动脉疾病。在这份关于癌症免疫治疗的心血管毒性的科学声明中，我们总结了 ICI、CAR-T、NK 和 TIL 疗法的病理生理学、流行病学、诊断和管理。我们还强调了文献中的差距以及未来研究应关注的重点。
