ICOS和ICOS连接体:瘤病患者的表达模式和结果
Mina Nikanjam1, Shumei Kato2, Daisuke Nishizaki2
1Division of Hematology-Oncology, University of California San Diego, 1200 Garden View Road, La Jolla, CA 92024, USA.
Therapeutic advances in medical oncology
|April 29, 2025
概括
高诱导性T细胞共刺激剂 (ICOS) 在晚期癌症中的表达没有预测接受免疫检查点抑制剂 (ICI) 的患者的结果. 根据瘤类型,ICOS表达有所不同,与其他免疫检查点相关,这表明ICI组合试验的定制免疫学分析.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 翻译研究是翻译研究.
背景情况:
- 诱导性T细胞共刺激剂 (ICOS) 和它的配体 (ICOSL) 在免疫反应中发挥双重作用,可能会调解刺激和抑制.
- 了解ICOS的表达模式及其与其他免疫检查点的关系对于优化癌症免疫治疗至关重要.
研究的目的:
- 研究ICOS在晚期/转移性癌症中的转录体表达模式.
- 确定ICOS表达与其他免疫检查点 (PD-1,PD-L1,CTLA-4) 的关联.
- 评估ICOS表达对患者结果的预后意义,包括无进展生存 (PFS) 和整体生存 (OS),特别是在免疫检查点抑制剂 (ICI) 治疗后.
主要方法:
- 追溯队列研究分析了来自514名患有晚期/转移性癌症的患者的RNA测序数据.
- ICOS和其他免疫检查点RNA表达被量化并分为高 (75-100百分位) 和低 (0-24百分位) 表达组.
- 统计分析包括费舍尔的精确测试,后勤回归,卡普兰-梅尔分析 (日志级别测试) 和考克斯的比例危险模型,以评估关联和生存结果.
主要成果:
- 在14%的队列中观察到高ICOSRNA表达,并且与高PD-1,PD-L1和CTLA-4RNA表达以及非结肠直肠癌诊断独立相关.
- ICOS和ICOSL表达模式在不同瘤类型和不同瘤类型中表现出显著的变化.
- 在接受ICI治疗的患者中 (n=217),高ICOS表达与改善PFS或OS没有显著相关. 同样,在以前没有接受免疫治疗的患者中 (n=272),ICOS表达没有影响OS.
结论:
- 高ICOS表达不是预后标记,也不能独立预测ICI治疗患者的结果.
- 观察到高ICOS与其他免疫检查点的相关性表明瘤微环境中的复杂相互作用.
- 在针对ICOS/ICOSL途径的临床试验中,对于患者选择,可能需要个性化瘤免疫学分析,特别是与ICI结合使用.
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