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CAR-T 细胞治疗中的外泌体与细胞外囊泡:心脏损伤的新兴介质与生物标志物

英文原题:Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.

查看英文原题

Exosomes and Extracellular Vesicles in CAR-T Cell Therapy: Emerging Mediators and Biomarkers of Cardiac Injury.

PubMed 2026/04/16(内容时间) Cardiol Rev Q2 · IF 3.2(JCR 2025)

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中文摘要

CAR-T 细胞疗法已改变了血液系统恶性肿瘤的结局,但常并发心血管毒性,尤其是在细胞因子释放综合征的情况下。尽管全身性炎症、内皮激活和心肌应激已被认为参与其中,但免疫激活与心脏损伤之间的机制联系仍不完全清楚。外泌体及其他细胞外囊泡(EVs)已成为免疫应答过程中细胞间通讯的关键介质,携带包括细胞因子、microRNAs、蛋白质和脂质在内的生物活性货物,可调节心血管功能。在CAR-T 治疗的背景下,来源于活化T细胞、肿瘤细胞和受损内皮的EVs可能放大炎症信号、促进内皮功能障碍,并直接导致心肌损伤。

重要的是,EVs可在外周血中检测到,并在CAR-T 相关毒性期间表现出浓度和货物的动态变化,使其成为心脏损伤早期检测、风险分层和预后判断的有前景的生物标志物。本综述综合了目前关于外泌体和EVs在CAR-T 治疗中生物发生、功能作用及心血管效应的证据,强调其作为机制介质和转化生物标志物的潜力。

我们还讨论了现有知识空白、EV表征中的技术挑战,以及将基于EV的诊断整合到心脏肿瘤学实践中的未来方向。

展开英文摘要原文

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed outcomes in hematologic malignancies but is frequently complicated by cardiovascular toxicity, most notably in the setting of cytokine release syndrome. While systemic inflammation, endothelial activation, and myocardial stress have been implicated, the mechanistic links between immune activation and cardiac injury remain incompletely understood.

Exosomes and other extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication during immune responses, carrying bioactive cargo including cytokines, microRNAs, proteins, and lipids that can modulate cardiovascular function. In the context of CAR-T therapy, EVs derived from activated T-cells, tumor cells, and injured endothelium may amplify inflammatory signaling, promote endothelial dysfunction, and contribute directly to myocardial injury.

Importantly, EVs are detectable in peripheral blood and exhibit dynamic changes in concentration and cargo during CAR-T-associated toxicities, positioning them as promising biomarkers for early detection, risk stratification, and prognostication of cardiac injury. This review synthesizes current evidence on the biogenesis, functional roles, and cardiovascular effects of exosomes and EVs in CAR-T therapy, highlighting their potential as mechanistic mediators and translational biomarkers.

We also discuss existing knowledge gaps, technical challenges in EV characterization, and future directions for integrating EV-based diagnostics into cardio-oncology practice.

论文信息

作者
Thukral J、Moudgil P、Sindhwani N、Mann A、Makkar S、Kaur J、Shah RK、Kaur H
第一作者单位
From the Department of Internal Medicine, New York Medical College/Landmark Medical Center, Woonsocket, RI.United States
通讯作者单位
Department of Medicine, New York Medical College and Westchester Medical Center, Valhalla, NY.United States
期刊
Cardiology in review2026 Apr 16
原文标识
PubMed 41986929 · DOI 10.1097/CRD.0000000000001246