Cytokine profiling of patients with immune checkpoint inhibitor-associated myocarditis: a pilot study

Although immune checkpoint inhibitors (ICIs) have demonstrated high efficacy against malignant tumors, immune-related adverse cardiovascular events remain a significant concern. ICI-associated myocarditis is rare but potentially fatal. Therefore, identifying biomarkers is crucial for patient selection and management during ICI therapy. This pilot study aimed to explore cytokine profiles associated with the development of ICI myocarditis and evaluate their predictive value.

This study included 16 patients treated with ICI (6 with myocarditis [myocarditis group] and 10 without myocarditis [control group]). Serum samples were collected before ICI initiation (baseline) and 2-3 weeks after the first cycle of ICI administration (before the second cycle). Semi-quantitative membrane-based cytokine array analysis was used to detect 80 human cytokines.

Serum IL-1β and IL-2 levels significantly increased, and CCL4, CXCL5, angiogenin, EGF, and IL-10 significantly decreased in both groups after ICI initiation compared to baseline. In contrast, baseline cytokine levels differed between the groups: 43 cytokines, including G-CSF, IL-6, and CXCL13, were significantly elevated, and IL-10 was decreased in the myocarditis group compared to controls. After ICI treatment, serum levels of 23 cytokines, including CXCL13, IL-6, and leptin, were significantly higher in the myocarditis group than in controls.

Cytokine profiles change dramatically at the onset of ICI-associated myocarditis. Baseline immune dysregulation and/or increased reactivity to ICI therapy may contribute to the development of myocarditis. However, further studies are required to confirm these findings.