CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advancing precision cardio-oncology: multimodal surveillance and stratified management of immunotherapy-induced cardiovascular toxicity.
Advancing precision cardio-oncology: multimodal surveillance and stratified management of immunotherapy-induced cardiovascular toxicity.
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免疫检查点抑制剂(ICI)和CAR-T 细胞疗法的出现彻底改变了肿瘤学,但其与严重心血管免疫相关不良事件(irAE)的关联日益增多。本叙述性综述全面探讨了免疫治疗相关心血管毒性的流行病学、病理生理机制、生物标志物、先进影像学及管理策略。ICI相关心肌炎是一种罕见但可能致命的并发症,多发生于治疗早期,尤其在联合方案中更为常见,而更广泛的心血管谱系还包括心包炎、心律失常、心力衰竭和加速性动脉粥样硬化。
The advent of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapies has revolutionized oncology but is increasingly associated with severe cardiovascular immune-related adverse events (irAEs). This narrative review comprehensively examines the epidemiology, pathophysiologic mechanisms, biomarkers, advanced imaging, and management strategies for immunotherapy-associated cardiovascular toxicities.
ICI-associated myocarditis is a rare but potentially fatal complication occurring early in therapy, particularly with combination regimens, while the broader cardiovascular spectrum also encompasses pericarditis, arrhythmias, heart failure, and accelerated atherosclerosis.
Mechanistically, preclinical data suggest that ICI-associated myocarditis is hypothesized to be mediated by autoreactive CD8+ T-cell cross-reactivity against shared cardiac antigens, macrophage expansion, and inflammatory cytokine signaling, whereas CAR-T cardiovascular toxicity appears to contribute primarily secondary to systemic cytokine release syndrome (CRS). For early detection and risk stratification, high-sensitivity cardiac troponin remains the foundational biomarker, complemented by advanced multimodal imaging such as global longitudinal strain (GLS) echocardiography, cardiac magnetic resonance (CMR), and emerging molecular positron emission tomography (PET).
High-dose systemic corticosteroids remain the first-line intervention for symptomatic ICI-associated myocarditis, with targeted therapies like abatacept and ruxolitinib showing promise for steroid-refractory cases. Ultimately, proactive risk factor assessment and multidisciplinary cardio-oncology surveillance are imperative to mitigate acute toxicities and long-term atherosclerotic risks, ensuring optimal patient outcomes.
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