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Immune Checkpoint Inhibitors Mediated Lymphocytic and Giant Cell Myocarditis: Uncovering Etiological Mechanisms
Rishi Rikhi1,2, Jaret Karnuta2, Muzna Hussain3
1Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, United States.
Abstract:
The advent of immune checkpoint inhibitors (ICIs) has revolutionized the field of oncology, but these are associated with immune related adverse events. One such adverse event, is myocarditis, which has limited the continued immunosuppressive treatment options in patients afflicted by the disease. Pre-clinical and clinical data have found that specific ICI targets and precipitate distinct myocardial infiltrates, consistent with lymphocytic or giant cell myocarditis. Specifically, it has been reported that CTLA-4 inhibition preferentially results in giant cell myocarditis with a predominately CD4+ T cell infiltrate and PD-1 inhibition leads to lymphocytic myocarditis, with a predominately CD8+ T cell infiltrate. Our manuscript discusses the latest literature surrounding ICI pathways and targets, while detailing proposed mechanisms behind ICI mediated myocarditis.
Insights
Immune checkpoint inhibitors (ICIs) can cause myocarditis, a serious adverse event. Different ICI targets, like CTLA-4 and PD-1, lead to distinct types of myocarditis with specific T cell infiltrates.
Area of Science:
- Oncology
- Immunology
- Cardiology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer treatment.
- Immune-related adverse events (irAEs) are a significant concern with ICIs.
- Myocarditis is a severe irAE that can limit ICI therapy.
Purpose of the Study:
- To review the latest literature on ICI pathways and targets.
- To detail proposed mechanisms of ICI-mediated myocarditis.
- To differentiate myocarditis subtypes based on ICI targets.
Main Methods:
- Literature review of pre-clinical and clinical data.
- Analysis of ICI targets and associated myocardial infiltrates.
- Discussion of proposed pathomechanisms.
Main Results:
- CTLA-4 inhibition is linked to giant cell myocarditis with CD4+ T cells.
- PD-1 inhibition is associated with lymphocytic myocarditis and CD8+ T cells.
- Distinct ICI targets precipitate specific patterns of myocardial inflammation.
Conclusions:
- Understanding ICI-mediated myocarditis is crucial for patient management.
- Specific ICI targets correlate with distinct myocarditis pathologies.
- Further research into ICI mechanisms can inform safer cancer immunotherapy.
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