Insight of immune checkpoint inhibitor related myocarditis

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2024-11-12 DOI:10.1016/j.intimp.2024.113559

Jin-kui Pi , Xiao-ting Chen , Yan-jing Zhang , Xue-mei Chen , Yin-chan Wang , Jia-yi Xu , Jin-han Zhou , Shuai-shuai Yu , Si-si Wu

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引用次数: 0

Abstract

As the understanding of immune-related mechanisms in the development and progression of cancer advances, immunotherapies, notably Immune Checkpoint Inhibitors (ICIs), have become integral in comprehensive cancer treatment strategies. ICIs reactivate T-cell cytotoxicity against tumors by blocking immune suppressive signals on T cells, such as Programmed Death-1 (PD-1) and Cytotoxic T-lymphocyte Antigen-4 (CTLA-4). Despite their beneficial effects, ICIs are associated with immune-related adverse events (irAEs), manifesting as autoimmune side effects across various organ systems. A particularly alarming irAE is life-threatening myocarditis. This rare but severe side effect of ICIs leads to significant long-term cardiac complications, including arrhythmias and heart failure, and has been observed to have a mortality rate of up to 50% in affected patients. This greatly limits the clinical application of ICI-based immunotherapy. In this review, we provide a comprehensive summary of the current knowledge regarding the diagnosis and management of ICI-related myocarditis. We also discuss the utility of preclinical mouse models in understanding and addressing this critical challenge.

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洞察与免疫检查点抑制剂相关的心肌炎。

随着人们对癌症发生和发展过程中免疫相关机制认识的不断深入，免疫疗法，尤其是免疫检查点抑制剂（ICIs），已成为癌症综合治疗策略中不可或缺的一部分。ICIs 通过阻断 T 细胞上的免疫抑制信号，如程序性死亡-1（PD-1）和细胞毒性 T 淋巴细胞抗原-4（CTLA-4），重新激活 T 细胞对肿瘤的细胞毒性。尽管 ICIs 具有有益的作用，但它也与免疫相关不良事件（irAEs）有关，表现为各器官系统的自身免疫副作用。危及生命的心肌炎是一种特别令人担忧的不良反应。ICIs 这种罕见但严重的副作用会导致严重的长期心脏并发症，包括心律失常和心力衰竭，据观察，受影响患者的死亡率高达 50%。这极大地限制了基于 ICI 的免疫疗法的临床应用。在这篇综述中，我们全面总结了目前有关 ICI 相关心肌炎诊断和治疗的知识。我们还讨论了临床前小鼠模型在理解和应对这一严峻挑战方面的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.