Single-cell transcriptomic analysis deciphers the inflammatory microenvironment characterized by CXCL9+ fibroblasts and ACKR1+ endothelial cells in immune-related myocarditis

作者：Boyu Sun, Ziyu Xun, Zixiang Zhou, Nan Zhang, Mingjian Piao, Chengjie Li, Jiongyuan Li, Shuofeng Li, Longhao Zhang, Xiangqi Chen, Hanping Wang, Haitao Zhao · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06551-x · 被引用次数：15 · 研究领域：Cancer Immunotherapy and Biomarkers、Cardiac Fibrosis and Remodeling、Single-cell and spatial transcriptomics

BACKGROUND: Immune-related myocarditis induced by immune checkpoint inhibitors (ICIs) is a rare immune-related adverse event (irAE) but is characterized by a high mortality rate. However, the specific pathological mechanisms underlying immune-related myocarditis remain largely unclear. In this study, we aimed to elucidate the inflammatory microenvironment within cardiac tissues affected by immune-related myocarditis at the single-cell level to identify potential therapeutic targets. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on an endomyocardial biopsy specimen obtained from a patient with pancreatic neuroendocrine carcinoma who developed immune-related myocarditis following treatment with ICIs. Additionally, the scRNA-seq data of heart specimens from deceased donors without cardiovascular diseases were collected and applied as normal control. To validate our findings and assess their specificity to ICI-related pathology, we analyzed mouse scRNA-seq data, including controls, ICI-related myocarditis, viral myocarditis, and autoimmune myocarditis. RESULTS: We found elevated proportions of lymphocytes, myeloid cells, and fibroblasts in the irAE group, suggesting an intensified inflammatory microenvironment in human immune-related myocarditis. Within the lymphocyte compartment, increased proportions of CD8 + T exhausted cells and CD8 + T proliferative cells were observed in the irAE group. The upregulated differentially expressed genes in myeloid cells in the ir...