An Interferon-γ-Driven Myeloid Inflammatory Signature defines Glucocorticoid-Resistance of Immune Checkpoint Inhibitor-Associated Myocarditis

Immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis) is a rare but severe immune-related adverse event characterized by myocardial inflammation and injury. Although high-dose glucocorticoids represent first-line therapy, a subset of patients exhibits persistent myocardial injury despite treatment. In this study, we analyzed a cohort of 74 patients with ICI-myocarditis and classified patients based on longitudinal high-sensitivity cardiac troponin T (hs-cTnT) trajectories following glucocorticoid initiation into glucocorticoid-sensitive (GC-S) and glucocorticoid-refractory (GC-R) groups. Clinical outcomes, including major adverse cardiac events (MACE), were assessed. To investigate underlying biological differences, single-nucleus RNA sequencing (snRNA-seq) was performed on endomyocardial biopsy samples from GC-S (n=2) and GC-R (n=4) patients. The dataset provides high-resolution transcriptional profiles of myocardial cell populations, enabling analysis of cellular composition and inflammatory signaling pathways associated with differential treatment response. This resource supports investigation of immune cell heterogeneity and transcriptional programs in ICI-myocarditis, with a focus on differences between glucocorticoid-sensitive and glucocorticoid-refractory disease states.