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并且是非小细胞肺癌免疫治疗的潜在靶点。 (原句缺少主语,根据语境推测翻译,但严格来说原句表述不完整)

and are potential targets of immunotherapy in non-small cell lung cancer.

作者信息

Gao Zhen, Han Rui, Chen Qinghao, Guo Jichao, Wang Yancheng, Hong Qian, Zhao Chenguang, Mu Juwei, Li Jiagen

机构信息

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Department of Thoracic Surgery, Shulan (Jinan) Hospital, Jinan, China.

出版信息

J Thorac Dis. 2025 Mar 31;17(3):1169-1184. doi: 10.21037/jtd-24-1589. Epub 2025 Mar 27.

Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) are clinically effective in the treatment of non-small cell lung cancer (NSCLC), but the response rate in nonselective NSCLC patients is approximately 20%. It is important to expand the pool of benefits of immunotherapy. However, current solution strategies are limited. Our research is to identify new targets for combined immunotherapy and expand the beneficiary population of immunotherapy.

METHODS

Functional enrichment analysis was performed for differentially expressed genes (DEGs) in 175 NSCLC immunotherapy cohorts and 494 non-immunotherapy cohorts, and single-sample gene set enrichment analysis (ssGSEA) was used to quantify the level of infiltration of different immune cell subpopulations. Weighted correlation network analysis (WGCNA), univariate Cox regressions, least absolute shrinkage and selection operator (LASSO) regressions, and gene correlation analysis were applied to identify immune signature genes associated with immune cell infiltration, and a nomogram was constructed to predict the survival rate.

RESULTS

The DEGs were not enriched in the classical antitumour immune response and the dendritic cells (DCs) infiltration level in the tumour microenvironment (TME) was at a low level in the immunotherapy cohort. The high expression of and was positively correlated with the level of DCs infiltration, the core of tumour immune response regulation, and can bring better survival prognosis for patients. Besides, targeted activation of and can improve the efficacy of ICIs.

CONCLUSIONS

High expression of and enhances the antitumour immune response, and and may be new prognostic indicators and targets of combined ICIs for lung adenocarcinoma in NSCLC.

摘要

背景

免疫检查点抑制剂(ICIs)在非小细胞肺癌(NSCLC)治疗中具有临床疗效,但非选择性NSCLC患者的缓解率约为20%。扩大免疫治疗的受益群体很重要。然而,目前的解决策略有限。我们的研究旨在识别联合免疫治疗的新靶点并扩大免疫治疗的受益人群。

方法

对175个NSCLC免疫治疗队列和494个非免疫治疗队列中的差异表达基因(DEGs)进行功能富集分析,并使用单样本基因集富集分析(ssGSEA)来量化不同免疫细胞亚群的浸润水平。应用加权基因共表达网络分析(WGCNA)、单变量Cox回归、最小绝对收缩和选择算子(LASSO)回归以及基因相关性分析来识别与免疫细胞浸润相关的免疫特征基因,并构建列线图以预测生存率。

结果

DEGs在经典抗肿瘤免疫反应中未富集,且免疫治疗队列中肿瘤微环境(TME)中的树突状细胞(DCs)浸润水平较低。[基因名称1]和[基因名称2]的高表达与DCs浸润水平呈正相关,DCs是肿瘤免疫反应调节的核心,并且可以为患者带来更好的生存预后。此外,靶向激活[基因名称1]和[基因名称2]可以提高ICIs的疗效。

结论

[基因名称1]和[基因名称2]的高表达增强了抗肿瘤免疫反应,[基因名称1]和[基因名称2]可能是NSCLC中肺腺癌联合ICIs的新预后指标和靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fd/11986741/aacf5459ffdc/jtd-17-03-1169-f1.jpg

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