Single‐cell RNA sequencing reveals the altered innate immunity in immune checkpoint inhibitor‐related myocarditis

Abstract Background Myocarditis has emerged as a rare but lethal Immune checkpoint inhibitor (ICI)-associated toxicity. However, the exact mechanism for ICI related myocarditis remains underexplored; and the specific therapeutic targets is still lacking. In this study, we used scRNA-seq to characterize the transcriptomic profiles of single cells from the peripheral blood mononuclear cell (PBMC) of ICI related myocarditis during fulminant myocarditis and disease recovery. Methods PBMC samples were taken from the patient during fulminant ICI related myocarditis and after disease remission. Cells were isolated from blood samples by density gradient centrifugation over Ficoll-Paque. Single-cell RNA sequencing with 10X genomics was performed. Subpopulation determination, functional analysis, single-cell trajectory and cell-cell interaction analysis were carried out afterwards. Results We presented the altered landscape of immune cells and differential genes in ICI related myocarditis during the disease activity and remission using scRNA-seq. Substantial immune cell composition and intercellular communication were found to be altered. Monocyte, NK cell as well as B cell subpopulations contributed to the regulation of innate immunity and inflammation in ICI related myocarditis. T cell subpopulations highly expressed genes associated with PD-1 inhibitor resistance and hyper-progressor. At last, the intercellular communication in ICI related myocarditis was significantly dysregulated. Conclusion By identifying altered pathways and highlighting a catalog of marker genes, this study has revealed the diversity of cellular populations in ICI related myocarditis, marked by their distinct transcriptional profiles and biological functions. Our investigation would shed light on the pathophysiological mechanism and potential therapeutic targets of ICI related myocarditis in continuous exploration.