| アブストラクト | BACKGROUND: Immune-checkpoint-inhibitor (ICI) have revolutionized cancer treatment but can trigger severe immune-related adverse events (irAEs). Among these, cardiovascular irAEs (CV-irAEs) are rare yet associated with particularly high morbidity and mortality. This study aims to characterize the clinical features and underlying molecular mechanisms of CV-irAEs using pharmacovigilance and single-cell RNA sequencing data. METHODS: CV-irAEs are identified in the FDA Adverse Event Reporting System (FAERS) database through disproportionality analysis using reporting odds ratios. Onset times are compared across clinical variables using non-parametric tests. Factors associated with fatal outcomes are evaluated by Fisher's exact test, whereas logistic regression is employed to identify predictors of CV-irAEs occurrence. Finally, single-cell RNA sequencing explores sex differences in myocarditis irAEs. RESULTS: Twenty-six cardiovascular toxicity events are identified as CV-irAEs. Over 55% of patients with CV-irAEs have indications of lung or skin cancer. Additionally, CV-irAEs have a 43.91% fatality rate, and 51.82% of patients experience CV-irAEs within one month of ICI therapy initiation. Notably, patients over 75 years of age and those receiving anti-PD-1 monotherapy or combination therapy with anti-CTLA-4 are more susceptible to developing CV-irAEs. Furthermore, males experience more severe CV-irAEs. Accordingly, single-cell analysis reveals enhanced MIF and CD99 signaling between dendritic cells and effector memory T cells in male myocarditis irAE patients, potentially explaining their greater susceptibility to severe CV-irAEs compared to females. CONCLUSIONS: We identify key clinical risk factors and a male-specific immune signature in CV-irAEs, providing a foundation for personalized risk assessment and further mechanistic studies. |
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| ジャーナル名 | European journal of pharmacology |
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| Pubmed追加日 | 2026/1/19 |
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| 投稿者 | Sang, Shaocong; Han, Huiming; Liu, Mingyue; Zhang, Nan; Cui, Yanrui; Liu, Kaidong; Xiong, Kai; Liang, Haihai; Lv, Lifang; Gu, Yunyan |
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| 組織名 | State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department;of Systems Biology, College of Bioinformatics Science and Technology, Harbin;Medical University, Harbin, China.;The Centre of Functional Experiment Teaching, School of Basic Medicine, Harbin;of Pharmacology (State Key Laboratory -Province Key Laboratories of;Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research,;Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin,;China.;Medical University, Harbin, China. Electronic address: lvlifanggaoqiang@163.com.;Medical University, Harbin, China. Electronic address: guyunyan@ems.hrbmu.edu.cn. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41548680/ |
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