The Role of Single-Cell Profiling and Deep Immunophenotyping in Understanding Immune Therapy Cardiotoxicity

Article Multidisciplinary Sciences

T cells specific for α-myosin drive immunotherapy-related myocarditis

Margaret L. Axelrod et al.

Summary: Immune checkpoint inhibitors (ICIs) used in anticancer therapy are challenged by immune-related adverse events, such as myocarditis. This study investigates the pathogenesis of ICI-associated myocarditis (ICI-MC) and identifies CD8(+)T cells as the major cell population involved. α-myosin, a cardiac-specific protein, is identified as a potential autoantigen in ICI-MC. Understanding the mechanisms of ICI-MC could lead to new strategies for preventing and treating ICI toxicity.

NATURE (2022)

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Article Cardiac & Cardiovascular Systems

Identification of Pathogenic Immune Cell Subsets Associated With Checkpoint Inhibitor-Induced Myocarditis

Han Zhu et al.

Summary: This study identified expanded cytotoxic CD8(+) Temra cells in the blood of patients with ICI myocarditis, which were clonally expanded and exhibited activated and cytotoxic phenotypes. These cells progressed into an exhausted phenotype after glucocorticoid treatment. The study also demonstrated the interaction between these expanded cells and innate immune cells, as well as the absence of key anti-inflammatory signals.

CIRCULATION (2022)

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Review Pharmacology & Pharmacy

Immune Checkpoint Inhibitor Cardiotoxicity: Understanding Basic Mechanisms and Clinical Characteristics and Finding a Cure

Sarah Waliany et al.

Summary: ICIs alter the immune system's response to cancerous tissues but can lead to varying degrees of autoimmunity, with cardiovascular complications such as myocarditis emerging as significant side effects. Understanding the mechanisms underlying these toxicities may help improve patient outcomes by reducing treatment-related morbidity.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021 (2021)

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Review Cardiac & Cardiovascular Systems

Mechanisms of Cardiovascular Toxicities Associated With Immunotherapies

Alan H. Baik et al.

Summary: Immune-based therapies have transformed cancer treatments, but cardiovascular complications arising from these therapies present new challenges in cardio-oncology. Understanding the mechanisms of immune activation and associated cardiovascular toxicities is crucial for addressing the cardiovascular sequelae of immunotherapy.

CIRCULATION RESEARCH (2021)

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Article Pharmacology & Pharmacy

Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment

Cong Wang et al.

Summary: By conducting a retrospective analysis of ICI-associated myocarditis, we identified two subgroups based on corticosteroid responsiveness: corticosteroid-sensitive and corticosteroid-resistant. Corticosteroid-resistant patients require larger doses and longer duration of corticosteroid treatment, with a higher mortality rate. The use of tofacitinib in corticosteroid-resistant patients may offer a new therapeutic option for ICI-associated myocarditis.

FRONTIERS IN PHARMACOLOGY (2021)

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Letter Cardiac & Cardiovascular Systems

RNA-Sequencing Reveals a Distinct Transcriptomic Signature for Giant Cell Myocarditis and Identifies Novel Druggable Targets

Kaushik Amancherla et al.

CIRCULATION RESEARCH (2021)

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Article Oncology

Comparative Transcriptomics of Immune Checkpoint Inhibitor Myocarditis Identifies Guanylate Binding Protein 5 and 6 Dysregulation

Daniel Finke et al.

Summary: Immune checkpoint inhibitors are transforming cancer treatment but can lead to immune-related adverse events, including ICI-associated myocarditis. The transcriptional alterations associated with this rare but severe phenomenon remain poorly characterized. By comparing transcriptomics, potential pathomechanisms like the GBP5 protein were identified that may help in diagnosing and identifying patients at risk for ICIM.

CANCERS (2021)

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Review Peripheral Vascular Disease

Single-Cell RNA Sequencing (scRNA-seq) in Cardiac Tissue: Applications and Limitations

Mingqiang Wang et al.

Summary: Cardiovascular diseases are the leading causes of death worldwide and their pathology is related to functional abnormalities of multiple cell types in the heart. Single-cell RNA sequencing technology is a powerful method to analyze individual cells and elucidate molecular mechanisms at a high resolution on a single-cell level.

VASCULAR HEALTH AND RISK MANAGEMENT (2021)

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Article Cardiac & Cardiovascular Systems