淋巴细胞激活基因-3与小细胞肺癌中的程序性死亡配体-1和程序性细胞死亡蛋白1相关。
Lymphocyte activation gene-3 is associated with programmed death-ligand 1 and programmed cell death protein 1 in small cell lung cancer.
作者信息
Sun Hui, Dai Jiawei, Zhao Lishu, Zhu Jun, Wang Hao, Chen Peixin, Lu Hui, Chen Qiankun, Zhang Zhemin
机构信息
Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
School of Medicine, Tongji University, Shanghai, China.
出版信息
Ann Transl Med. 2021 Sep;9(18):1468. doi: 10.21037/atm-21-4481.
BACKGROUND
In recent years, immunotherapy has achieved notable success in cancer treatment. Indeed, the novel immune checkpoint lymphocyte activation gene-3 (LAG3) has shown promising therapeutic efficacy in non-small cell lung cancer. However, it is unclear about the role of LAG3 in immunotherapy and survival in small cell lung cancer (SCLC).
METHODS
The expression of LAG3 in SCLC was evaluated in four public datasets. The association of LAG3 with programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and overall survival (OS) was investigated. The LAG3-related biological processes and pathways were identified by functional analyses.
RESULTS
LAG3 expression was detected in SCLC tumor tissues. In the cBioPortal dataset with 81 clinical SCLC samples, LAG3 expression was markedly associated with PD-1 and PD-L1 expression (both P<0.050). In addition, Patients with high LAG3 expression had a trend toward a better OS (P=0.073). A similar survival trend was also observed in the GSE60052 dataset. Significantly, LAG3 expression was related to immune-related biological processes, such as immune response, antigen processing and presentation, and T cell co-stimulation (all P<0.001).
CONCLUSIONS
This study demonstrated that LAG3 is an important immune checkpoint that is closely associated with PD-1/PD-L1. LAG3 may be a promising novel immunotherapy target for SCLC.
背景
近年来，免疫疗法在癌症治疗中取得了显著成功。事实上，新型免疫检查点淋巴细胞激活基因3（LAG3）在非小细胞肺癌中已显示出有前景的治疗效果。然而，LAG3在小细胞肺癌（SCLC）的免疫治疗及生存中的作用尚不清楚。
方法
在四个公共数据集中评估LAG3在SCLC中的表达。研究LAG3与程序性死亡配体1（PD-L1）、程序性细胞死亡蛋白1（PD-1）及总生存期（OS）的关联。通过功能分析确定与LAG3相关的生物学过程和通路。
结果
在SCLC肿瘤组织中检测到LAG3表达。在包含81例临床SCLC样本的cBioPortal数据集中，LAG3表达与PD-1和PD-L1表达显著相关（均P<0.050）。此外，LAG3高表达患者有总生存期更好的趋势（P=0.073）。在GSE60052数据集中也观察到类似的生存趋势。值得注意的是，LAG3表达与免疫相关生物学过程有关，如免疫反应、抗原加工和呈递以及T细胞共刺激（均P<0.001）。
结论
本研究表明LAG3是一个与PD-1/PD-L1密切相关的重要免疫检查点。LAG3可能是SCLC一种有前景的新型免疫治疗靶点。
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