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在小细胞肺癌中LAG-3的表达和临床影响

Liangdong Sun¹, Junjie Hu¹, Jue Wang¹

¹Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

|September 17, 2025

概括

淋巴细胞激活基因3 (LAG-3) 在小细胞肺癌 (SCLC) 中表达更高,并可能预测免疫治疗反应. 较高的LAG-3水平与改善的生存率相关,可以作为SCLC治疗的新生物标志物.

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) 在小细胞肺癌 (SCLC) 中表现有前途,但持久反应有限.
在SCLC中PD-L1的低表达表明其他免疫检查点可能是ICI的相关目标.

研究的目的:

评估SCLC中28个免疫检查点分子的表达.
为了确定在SCLC中用于ICI治疗的PD-L1以外的潜在生物标志物.
评估淋巴细胞激活基因3 (LAG-3) 作为SCLC免疫疗法疗效的预测标记.

主要方法:

来自细胞系的RNA-seq数据的分析 (癌细胞系百科全书).
来自瘤样本的蛋白质基因组和公共数据集 (微阵列,RNA-seq,scRNA-seq) 的评估.
免疫组织化学证实SCLC中的LAG-3表达.
使用的IMpower133和罗珀等人. 数据集来评估LAG-3的预测价值.

主要成果:

与其他癌症相比,SCLC细胞系中的LAG-3表达显著更高.
在SCLC瘤中,LAG-3是最过度表达的检查点分子,而不是配对的正常样本.
较高的LAG-3表达与较长的整体存活率相关,是独立的有利预后因素.
与增加的MHC-I,免疫细胞透和其他免疫检查点相关的LAG-3表达.
在瘤细胞和T细胞,特别是CD8+T细胞上的LAG-3表达高于PD-1,CD274和CTLA-4.
增加LAG-3表达与SCLC患者ICI治疗的益处相关.

结论:

在SCLC中LAG-3的表达很高,可以作为免疫治疗的潜在预测生物标志物.
针对LAG-3可能是一个有希望的策略,以改善SCLC患者的ICI疗效.

关键词:

现场行动小组-3 免疫疗法免疫疗法预后预后预后小细胞肺癌是一种小细胞肺癌.瘤免疫微环境是一个微环境.

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