针对LLT1作为癌症患者的潜在免疫疗法选择,在多个固体瘤中对现有的检查点疗法没有反应
Tirtha Mandal1, Soorya Gnanasegaran1, Golding Rodrigues2
1Zumutor Biologics, Bangalore, Karnataka, India.
BMC cancer
|November 7, 2024
概括
高LLT1表达与免疫抑制性瘤微环境 (TME) 和许多癌症的不良预后相关. 准LLT1可能会改善对免疫检查点抑制剂 (ICI) 无反应的患者的反应.
科学领域:
- 免疫学和癌症研究
- 分子生物学和基因组学
背景情况:
- 在各种癌症中观察到高水平的莱克样转录1 (LLT1),它通过与自然杀手 (NK) 细胞上的CD161相互作用来促进瘤免疫逃生.
- 准LLT1提供了一种潜在的策略,以克服免疫逃避并增强NK细胞介导的抗瘤免疫力.
研究的目的:
- 通过使用癌症基因组图谱 (TCGA) 数据库,研究LLT1在广泛的癌症中瘤微环境 (TME) 中的作用.
- 确定LLT1作为预测患者预后和免疫疗法反应的潜在生物标志物.
主要方法:
- 使用TCGA转录组数据分析了33种癌症类型的LLT1表达.
- 与患者存活率,免疫细胞透,免疫基因特征和癌症基因组生物标志物 (TMB,MSI,MMR) 通过单变Cox回归相关联的LLT1表达.
- 使用免疫光学验证了LLT1表达,并使用CRI iAtlas数据评估了其与免疫检查点抑制剂 (ICI) 不响应的队列的相关性.
主要成果:
- 在12种癌症中发现LLT1表达升高,与COAD,KICH和KIRC的预后不佳有关.
- 上调的LLT1与增加的NK和T细胞透,免疫疲劳标记物以及TME中的基因组生物标记物相关.
- 通过免疫光和临床队列分析证实,LLT1表达与不响应当前ICI的患者的免疫抑制基因有关.
结论:
- 增加LLT1表达是多种癌症类型中免疫抑制性TME的生物标志物.
- LLT1代表了一个有前途的治疗标,用于提高对ICI无反应的LLT1升调患者的临床反应.
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