Immune Checkpoint Inhibitors Mediated Lymphocytic and Giant Cell Myocarditis: Uncovering Etiological Mechanisms

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.