与免疫相关不良事件相关的先天性和适应性免疫特征
Shaheen Khan1, Venkat S Malladi2,3, Mitchell S von Itzstein4,5
1Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA David.Gerber@utsouthwestern.edu shaheenmkhan@outlook.com.
预先存在的自身免疫状况,由特定的免疫细胞和炎症标记物标记,预测免疫检查点抑制剂 (ICI) 治疗期间的免疫相关不良事件 (irAEs). 了解这些基线免疫特征可以帮助预测和潜在地减轻irAEs.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 翻译医学是一种翻译医学.
背景情况:
- 免疫检查点抑制剂 (ICI) 是有效的癌症治疗方法,但可能导致严重的免疫相关不良事件 (irAEs).
- 了解iRAE背后的生物机制对于患者安全和治疗优化至关重要.
研究的目的:
- 在接受ICI治疗的患者中,与irAE发展相关的外周免疫景观的特征.
- 为了确定潜在的生物标志物来预测irAEs.
主要方法:
- 多维分析包括单细胞RNA测序,质量细胞计,细胞因子测定和抗核抗体 (ANA) 分析.
- 在接受ICI治疗的162名患者中,表征周边免疫细胞和基因表达,比较具有和没有irAEs的患者.
主要成果:
- 患有irrAEs的患者表现出基线前炎症性,自身免疫性状况,CD57+ T/NK细胞,血质细胞,活性淋巴细胞和ANA水平升高.
- 在irAE患者中观察到明显的基线促炎基因特征 (例如IL1B,CXCL8,CXCR3,TNF,IFNG) 和丰富的TNF信号.
- 没有irrAEs的患者有增加的基线免疫抑制标志物和明显的髓状细胞重编程.
结论:
- 一个先前存在的被激活的,类似于自身免疫的促炎状态通过血细胞/ANA,IFN-玛/CXCL10/CXCR3和TNF信号轴驱动irAE的发展.
- 这些发现表明,潜在的外周免疫生物标志物可用于预测irAE.
- 该研究提供了对irAE机制的生物学见解,可能指导缓解策略.
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