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作为免疫相关不良事件的预测因素的T细胞耐受分数

Jared Ostmeyer¹, Jason Y Park², Mitchell S von Itzstein³

¹Peter O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Journal for immunotherapy of cancer

|August 14, 2023

概括

一种新的T细胞耐受性分量指标可以预测接受免疫检查点抑制剂 (ICI) 治疗的患者的严重免疫相关不良事件 (irAEs). 这一发现为管理ICI诱导的毒性提供了潜在的生物标志物.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物标志物发现发现

背景情况:

免疫检查点抑制剂 (ICI) 疗法可能导致严重的自身免疫副作用,称为免疫相关不良事件 (irAEs).
在ICI疗效和毒性方面,T细胞起着至关重要的作用,这表明T细胞分析可以预测irAE风险.

研究的目的:

评估一种新型指标,即T细胞耐受性分数,作为接受ICI治疗的患者未来irAEs的预测指标.
为了比较T细胞耐受性分数与传统的T细胞受体β (TRB) 克隆性和多样性指标的预测性能.

主要方法:

在接受ICI治疗的77名癌症患者的基线预治疗样本上进行了T细胞受体β (TRB) 位测序.
计算T细胞耐受性分数并评估其预测临床显著irrAEs的能力 (CTCAE等级≥2vs0-1).
耐受性分数进一步分析了针对自身抗原napsin A丰富的T细胞,胸膜T细胞与外周血液T细胞以及针对各种自身免疫疾病的T细胞.

主要成果:

在患有临床显著的irrAEs (AUC = 0.79,p<0.001) 的患者中,T细胞耐受率显著降低 (AUC = 0.79,p<0.001).
这种预测值在不同的ICI类型中观察到,尤其是CTLA4抑制剂.
耐受性分数在准自身抗原纳素A的T细胞和胸膜T细胞中也较低,这表明与自我耐受性机制的联系.

结论:

基线T细胞耐受性分数显示为ICI治疗患者临床显著的irAEs的预测生物标志物.
这一新型指标可能有助于识别具有较高IRE风险的患者,并可能指导治疗策略和患者管理.

关键词:

这是一种自身免疫力.免疫耐受性免疫耐受性免疫治疗是一种免疫疗法.的T-淋巴细胞.翻译医学研究翻译医学研究

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