Mediators and mechanisms of immune checkpoint inhibitor‐associated myocarditis: Insights from mouse and human

Immunological Reviews, Journal Year: 2023, Volume and Issue: 318(1), P. 70 - 80

Published: July 14, 2023

The broad application of immune checkpoint inhibitors (ICIs) has led to significant gains in cancer outcomes. By abrogating inhibitory signals, ICIs promote T cell targeting cells but can frequently trigger autoimmune manifestations, termed immune-related adverse events (irAEs), affecting essentially any organ system. Among cardiovascular irAEs, myocarditis (irMyocarditis) is the most described and carries highest morbidity. currently recommended treatment for irMyocarditis potent immunosuppression with corticosteroids other agents, this limited evidence basis. cellular pathophysiology remains poorly understood, though mouse models human data have both implicated effector CD8

Language: Английский

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APLAID complicated with arrhythmogenic dilated cardiomyopathy caused by a novel PLCG2 variant

Immunologic Research, Journal Year: 2024, Volume and Issue: 72(3), P. 512 - 519

Published: Jan. 19, 2024

Language: Английский

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Murine MHC-Deficient Nonobese Diabetic Mice Carrying Human HLA-DQ8 Develop Severe Myocarditis and Myositis in Response to Anti–PD-1 Immune Checkpoint Inhibitor Cancer Therapy

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 212(8), P. 1287 - 1306

Published: March 1, 2024

Myocarditis has emerged as an immune-related adverse event of immune checkpoint inhibitor (ICI) cancer therapy associated with significant mortality. To ensure patients continue to safely benefit from life-saving therapy, understanding fundamental immunological phenomena underlying ICI myocarditis is essential. We recently developed the NOD-cMHCI/II-/-.DQ8 mouse model that spontaneously develops lower mortality than observed in previous HLA-DQ8 NOD strains. Our strain was rendered murine MHC class I and II deficient using CRISPR/Cas9 technology, making it a genetically clean platform for dissecting CD4+ T cell-mediated absence classically selected CD8+ cells. These mice are highly susceptible acute heart failure following anti-PD-1 ICI-induced treatment. Additionally, administration accelerates skeletal muscle myositis. Using histology, flow cytometry, adoptive transfers, RNA sequencing analyses, we performed thorough characterization cardiac cells, identifying shared unique characteristics both populations. Taken together, this report details features rare, but lethal clinical presentation overlapping myositis therapy. This study sheds light on mechanisms provides basis further detailed analyses diagnostic therapeutic strategies.

Language: Английский

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The PD-1–PD-L1 pathway maintains an immunosuppressive environment essential for neonatal heart regeneration

Nature Cardiovascular Research, Journal Year: 2024, Volume and Issue: 3(3), P. 389 - 402

Published: March 1, 2024

Language: Английский

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Exploring T Cell Receptor Repertoires in Myocardial Diseases

Circulation Research, Journal Year: 2024, Volume and Issue: 134(12), P. 1808 - 1823

Published: June 6, 2024

Mounting experimental and clinical evidence has revealed that adaptive immune mechanisms targeting myocardial antigens are triggered by different forms of cardiac injury impact disease progression. B T lymphocytes recognize specific via unique receptors generated through a somatic rearrangement process generates potential repertoire 10

Language: Английский

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