在接受免疫治疗的固体瘤患者中,与免疫相关的事件与Th17和Th2签名有关
Chester J Kao1, Soren Charmsaz1, Stephanie L Alden2
1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, a member of the imCORE network, Baltimore, Maryland, USA.
The Journal of clinical investigation
|October 15, 2024
概括
免疫检查点抑制剂 (ICI) 可以引起与免疫相关的不良事件 (irAEs). 早期免疫系统的变化,特别是T助手17和T助手2细胞,预测癌症患者的irAE发展.
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:
- 与免疫相关的不良事件 (irAEs) 对接受免疫检查点抑制剂 (ICI) 治疗的患者来说是一个重大问题.
- 了解IRE的早期驱动因素对于风险分层和开发干预措施至关重要.
- 需要进行前性全瘤评估,以确定各种癌症类型的irAE预测因子.
研究的目的:
- 在接受ICI的各种固体瘤患者中前性地研究irAEs的免疫驱动因素.
- 确定与临床显著的irAEs发展相关的早期生物标志物.
- 探索免疫细胞概况,细胞因子特征和irAE发生之间的关系.
主要方法:
- 一项观察性研究招募了111名接受固体瘤标准ICI治疗的患者.
- 在基线和治疗期间采集了血液样本,用于细胞因子分析 (Luminex) 和免疫细胞分析 (CyTOF).
- 在整个治疗过程中,定期进行对irAEs的临床评估.
主要成果:
- 40.5%的患者出现了与ICI联合使用和先前自身免疫性疾病相关的症状性irrAEs (等级≥2).
- 早期Th17 (IL-6,IL-17f) 和2型 (IL-5,IL-13,IL-25) 细胞因子的增加,以及Th1 (TNF-α) 信号,与irAE发展相关.
- 在治疗过程中,Th17和Th2效应器记忆T细胞 (Th2EM) 的扩张也与更高等级的irAEs有关;高IL-6预测生存率较差.
结论:
- 在ICI治疗期间,早期的Th17和Th2免疫倾斜与全瘤环境中的irAE发展有关.
- 这些免疫特征预测了irAEs,但不是抗瘤反应,暗示了潜在的治疗点.
- 监测特定的细胞因子和T细胞种群可能有助于管理irAEs并改善患者的治疗结果.
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