Wu Yujuan, Gao Diansa, Tan Li, Chen Zhulu, Zhang Chuan, Mao Min, Zhu Yuxi, Liu Yue, Zuo Zhong
Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Oncol. 2025 Jul 16;15:1556373. doi: 10.3389/fonc.2025.1556373. eCollection 2025.
Peripheral immune cells can predict responses to immune checkpoint inhibitor (ICI) therapy, but their relationship with early ICI-associated cardiovascular adverse events (CVAEs) is unclear. This study aimed to assess the predictive value of peripheral immune cells in early ICI-associated CVAEs.
Single-cell RNA sequencing (scRNA-seq) dataset from the Gene Expression Omnibus database was used to explore immune cell changes associated with ICI-associated CVAEs. Patients who had received ICI therapy for three cycles at the First Affiliated Hospital of Chongqing Medical University between November 2020 and November 2022 were then included. Patients were stratified into CVAEs and no CVAEs groups and compared peripheral immune cell subsets. Univariate and multivariate regression analyses were conducted to identify CVAEs risk factors. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values for potential biomarkers. Propensity score matching (PSM) was used to validate the predictive value of baseline NK cell proportion for CAVEs.
ScRNA-seq data revealed decreased CD8+ T and B cell proportions in the CVAEs group, while NK cell proportions increased. Among 203 patients, dynamic changes in the proportion of total T cell, CD8+ T cell, and NK cell differed significantly between groups. Baseline NK cell proportion was identified as an independent risk factor for CVAEs (p=0.009). ROC analysis identified baseline NK cell proportion as a potential predictor of CVAEs (AUC 0.674). The optimal cutoff value was determined to be 16.4%, and this finding was confirmed following PSM.
Baseline NK cell proportion was a potential predictor of early ICI-associated CVAEs.
外周免疫细胞可预测免疫检查点抑制剂（ICI）治疗的反应，但其与早期ICI相关心血管不良事件（CVAEs）的关系尚不清楚。本研究旨在评估外周免疫细胞在早期ICI相关CVAEs中的预测价值。
使用基因表达综合数据库中的单细胞RNA测序（scRNA-seq）数据集，探索与ICI相关CVAEs相关的免疫细胞变化。然后纳入2020年11月至2022年11月期间在重庆医科大学附属第一医院接受三个周期ICI治疗的患者。将患者分层为CVAEs组和无CVAEs组，并比较外周免疫细胞亚群。进行单因素和多因素回归分析以确定CVAEs的危险因素。采用受试者工作特征（ROC）曲线分析确定潜在生物标志物的最佳截断值。使用倾向评分匹配（PSM）来验证基线NK细胞比例对CAVEs的预测价值。
scRNA-seq数据显示，CVAEs组中CD8 + T细胞和B细胞比例降低，而NK细胞比例增加。在203例患者中，总T细胞、CD8 + T细胞和NK细胞比例的动态变化在两组之间存在显著差异。基线NK细胞比例被确定为CVAEs的独立危险因素（p = 0.009）。ROC分析确定基线NK细胞比例为CVAEs的潜在预测指标（AUC 0.674）。最佳截断值确定为16.4%，PSM后这一发现得到证实。
基线NK细胞比例是早期ICI相关CVAEs的潜在预测指标。
