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检查点心肌炎中的免疫反应遍及心脏,血液和瘤
Steven M Blum1,2,3,4, Daniel A Zlotoff1,3,4,5, Neal P Smith1,2,3
1Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
bioRxiv : the preprint server for biology
|October 4, 2023
概括
免疫检查点抑制剂可以导致严重的心肌炎. 这项研究揭示了关键的免疫细胞和相关途径,确定了肌心炎患者致命结局的血液生物标志物.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 心脏病学 心脏病学
背景情况:
- 免疫检查点抑制剂 (ICI) 是关键的癌症疗法,但可以引发严重的免疫相关不良事件 (irAEs).
- 与ICI相关的心肌炎 (irMyocarditis) 是一种罕见但高度致命的irAE,其机制和与抗瘤免疫的联系尚不清楚.
研究的目的:
- 鉴定心肌炎患者心脏,瘤和血液中的免疫反应.
- 为了确定与irMyocarditis临床严重程度和死亡率相关的生物标志物.
- 为了阐明irMyocarditis的发病原因.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和T细胞受体 (TCR) 的测序.
- 显微镜和蛋白质组学分析.
- 对28名心肌炎患者和23名对照组进行了比较分析.
主要成果:
- 鉴定细胞毒性T细胞,炎症性巨细胞,树突细胞和纤维细胞在心肌炎中丰富的心脏组织.
- 在多种细胞类型中促进炎症转录程序的升级.
- 在心脏和瘤组织中具有独特的T细胞受体谱,在循环的CD8T细胞中发现心脏扩展的TCR作为潜在的致死生物标志物.
结论:
- 阐明了导致肌心炎发病的关键生物机制.
- 突出了潜在的治疗目标,并确定了一种用于预测致命结果的新型外围生物标志物.
- 对抗瘤免疫和与免疫相关的不良事件之间的复杂相互作用的高级理解.
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