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NK 细胞作为早期免疫检查点抑制剂相关心血管不良事件的潜在预测生物标志物:一项回顾性队列研究

英文原题:Natural killer cell as a potential predictive biomarker for early immune checkpoint inhibitor-associated cardiovascular adverse events: a retrospective cohort study.

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Natural killer cell as a potential predictive biomarker for early immune checkpoint inhibitor-associated cardiovascular adverse events: a retrospective cohort study.

PubMed 2025/07/16(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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研究概要

基线 NK 细胞比例是早期 ICI 相关 CVAEs 的潜在预测因子。

研究思路结论见上方概要

外周免疫细胞可以预测对免疫检查点抑制剂 (ICI) 治疗的反应,但它们与早期 ICI 相关心血管不良事件 (CVAE) 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 CVAE 中的预测价值。

来自基因表达综合数据库的单细胞 RNA 测序 (scRNA-seq) 数据集用于探索与 ICI 相关的 CVAE 相关的免疫细胞变化。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3个周期ICI治疗的患者。将患者分为 CVAE 组和无 CVAE 组,并比较外周免疫细胞亚群。进行单变量和多变量回归分析以确定 CVAE 危险因素。受试者工作特征 (ROC) 曲线分析确定了潜在生物标志物的最佳截止值。倾向评分匹配 (PSM) 用于验证基线 NK 细胞比例对 CAVE 的预测价值。

单细胞RNA测序数据显示,CVAEs组CD8+ T细胞和B细胞比例降低,而NK细胞比例升高。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的潜在预测因子(AUC 0.674)。最佳截断值确定为16.4%,该发现在PSM后得到证实。

展开英文摘要原文

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.

论文信息

作者
Wu Y、Gao D、Tan L、Chen Z、Zhang C、Mao M、Zhu Y、Liu Y
单位
Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.China
期刊
Frontiers in oncology2025
原文标识
PubMed 40740863 · DOI 10.3389/fonc.2025.1556373