| アブストラクト | BACKGROUND: Immune checkpoint inhibitor (ICI)-associated myocarditis (ICI-M) is a rare but potentially lethal immune-related adverse event (irAE). Early identification of fulminant (severe) cases remains challenging, and the peripheral immune derangements underlying ICI-M are incompletely characterized. METHODS: The disproportionality analysis was performed using the FDA Adverse Event Reporting System (FAERS) database (2015-2026) for patients treated with eight ICIs. A retrospective cohort of 100 patients who developed ICI-M was stratified into severe and non-severe groups. Peripheral blood cells and their derived ratio index were analyzed. A severity-predictive nomogram was developed using features selected by three machine learning methods, and was evaluated by calibration, receiver operating characteristic, and decision curve analyses. Single-cell RNA-seq data from peripheral blood mononuclear cells were analyzed to explore immune landscape alterations for ICI-M. RESULTS: FAERS analysis revealed strong signals for ICI-M across all eight ICIs, with >80% of cases occurring within three months of therapy. Associations between peripheral blood cells/derived ratio indexes and ICI-M were identified: the (neutrophil + monocyte) to lymphocyte ratio (NMLR), cTnI, and NT-proBNP were identified as key predictors of severe ICI-M. The 3-feature-based exploratory nomogram demonstrated a relatively good predictive performance (Area under curve = 0.849) with internal validation performed via 1000 bootstrap samples. Single-cell profiling identified monocyte expansion and lymphocyte contraction for ICI-M and its severity. The pseudotime ordering, ligand-receptor inference, subcluster differential abundance analysis, and pathway enrichment analyses associated a distinct FCGR3A + monocyte subset with a potential role in ICI-M development. CONCLUSION: This study provides a multi-dimensional view of ICI-M, integrating clinical and single-cell immune profiling analysis of peripheral blood cells as well as pharmacovigilance data. The developed nomogram may serve as a potential tool for identifying severe ICI-M, although external validation in independent cohorts is warranted. Insight into the immune landscape may inform future therapeutic strategies targeting specific cell-cell interactions in ICI-M. |
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| ジャーナル名 | Frontiers in immunology |
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| Pubmed追加日 | 2026/9/10 |
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| 投稿者 | Li, Zhenli; He, Jing; Ma, Zipei; Liu, Piaoran; Guan, Zhengkun; Du, Shaoyan; Yao, Tiezhu; Liu, Guang; Liu, Jing; Guo, Ling; Zhang, Yaozhong; Wang, Tenghui; Li, Mengjia; Ma, Jingtao |
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| 組織名 | Department of Cardiology, The Fourth Hospital of Hebei Medical University/The;Tumor Hospital of Hebei Province, Shijiazhuang, Hebei, China.;Hebei Medical University, Shijiazhuang, Hebei, China.;Department of Cardiology, Peking University International Hospital,;Beijing, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42718552/ |
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