LAG-3的转录体表达与其他检查点线性相关,但与临床结果无关
Jacob J Adashek1, Shumei Kato2, Daisuke Nishizaki2
1Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital Baltimore, MD 21287, USA.
American journal of cancer research
|February 7, 2024
概括
高水平的淋巴细胞激活基因3 (LAG-3) 表达并不能预测癌症患者对PD-1/PD-L1检查点阻塞的抵抗力. 然而,LAG-3与其他检查点的共同表达模式可能会指导组合免疫疗法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 免疫检查点抑制剂 (ICI) 已经改变了癌症治疗.
- 多omics方法,包括下一代测序,识别治疗点和免疫媒介.
- 淋巴细胞激活基因3 (LAG-3) 是新型癌症免疫疗法的目标,其中有一种FDA批准的抑制剂和其他正在开发中的抑制剂.
研究的目的:
- 分析淋巴细胞激活基因3 (LAG-3) 在各种癌症类型中的转录体表达.
- 评估LAG-3表达在晚期恶性瘤患者的预后和预测价值.
- 探索LAG-3表达与PD-L1,PD-1和CTLA-4等其他免疫检查点之间的关系.
主要方法:
- 在514名患有各种癌症的患者中对LAG-3表达的转录组分析.
- 在LAG-3RNA水平与其他免疫检查点RNA水平 (PD-L1,PD-1,CTLA-4) 之间的相关性分析.
- 卡普兰-梅尔和多变量分析,以评估LAG-3作为免疫治疗先前和治疗患者的整体生存 (OS) 和无进展生存 (PFS) 的预后因素.
主要成果:
- 在癌症类型之间和癌症类型内,LAG-3的转录基因表达有显著的变化.
- LAG-3RNA水平与PD-L1,PD-1和CTLA-4RNA水平呈现弱线性相关性.
- 高LAG-3表达不是免疫治疗先验患者中OS的预后因素.
- 单变量分析表明高LAG-3水平与抗PD-1/PD-L1治疗后更长的生存寿命相关,但这在多变量分析中没有显著意义.
结论:
- 单靠高LAG-3表达不能预测抗PD-1/PD-L1检查点阻塞的抗性.
- LAG-3通常与PD-1,PD-L1和CTLA-4共同表达.
- 调查LAG-3的免疫共同表达模式可能会确定受益于组合检查点阻塞疗法的患者群体.
相关概念视频
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...


