晚期非小细胞肺癌中肿瘤相关中性粒细胞的单细胞谱分析

IF 5.1 Q1 ONCOLOGY
Lung Cancer: Targets and Therapy Pub Date : 2023-11-21 eCollection Date: 2023-01-01 DOI:10.2147/LCTT.S430967
Jinpeng Shi, Jiayu Li, Haowei Wang, Xuefei Li, Qi Wang, Chao Zhao, Lei Cheng, Ruoshuang Han, Peixin Chen, Haoyue Guo, Zhuoran Tang, Caicun Zhou, Zhemin Zhang, Fengying Wu
{"title":"晚期非小细胞肺癌中肿瘤相关中性粒细胞的单细胞谱分析","authors":"Jinpeng Shi, Jiayu Li, Haowei Wang, Xuefei Li, Qi Wang, Chao Zhao, Lei Cheng, Ruoshuang Han, Peixin Chen, Haoyue Guo, Zhuoran Tang, Caicun Zhou, Zhemin Zhang, Fengying Wu","doi":"10.2147/LCTT.S430967","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.</p><p><strong>Materials and methods: </strong>We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.</p><p><strong>Results: </strong>Seven distinct TAN subtypes were defined, of which, the N<sub>3</sub> cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N<sub>3</sub> might be a pro-tumorigenic TAN subtype. N<sub>1</sub> and N<sub>5</sub> clusters were considered to be well differentiated and mature neutrophils based on <i>CXCR2</i> expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.</p><p><strong>Conclusion: </strong>Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676108/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.\",\"authors\":\"Jinpeng Shi, Jiayu Li, Haowei Wang, Xuefei Li, Qi Wang, Chao Zhao, Lei Cheng, Ruoshuang Han, Peixin Chen, Haoyue Guo, Zhuoran Tang, Caicun Zhou, Zhemin Zhang, Fengying Wu\",\"doi\":\"10.2147/LCTT.S430967\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.</p><p><strong>Materials and methods: </strong>We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.</p><p><strong>Results: </strong>Seven distinct TAN subtypes were defined, of which, the N<sub>3</sub> cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N<sub>3</sub> might be a pro-tumorigenic TAN subtype. N<sub>1</sub> and N<sub>5</sub> clusters were considered to be well differentiated and mature neutrophils based on <i>CXCR2</i> expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.</p><p><strong>Conclusion: </strong>Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.</p>\",\"PeriodicalId\":18066,\"journal\":{\"name\":\"Lung Cancer: Targets and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2023-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676108/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lung Cancer: Targets and Therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2147/LCTT.S430967\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lung Cancer: Targets and Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/LCTT.S430967","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:中性粒细胞在恶性肿瘤的发生和发展中起着不可忽视的调节作用,在这一过程中起着双重作用。因此,在单细胞分辨率上全面了解晚期非小细胞肺癌(NSCLC)中肿瘤相关中性粒细胞(TANs)的异质性是必要和迫切的。材料和方法:我们使用9个新获得的标本,应用单细胞rna测序(scRNA-seq)来描绘晚期NSCLC中TANs亚型特异性转录组景观。进一步处理scRNA-seq数据进行伪时间分析,以描述TANs的发展轨迹。同时,通过细胞间相互作用分析揭示了肿瘤微环境(tumor microenvironment, TME)中TANs与其他类型细胞之间的相互作用。结果:确定了7种不同的TAN亚型,其中N3簇被认为是炎症表型,表达编码多种趋化细胞因子的基因,并且与较低的总生存率相关,表明N3可能是促肿瘤的TAN亚型。基于CXCR2的表达和假时间模式,N1和N5集群被认为是分化良好的成熟中性粒细胞,它们在肺腺癌中占相对较高的比例。此外,还发现了与中性粒细胞分化相关的基因。我们还发现,TAN亚型通过TME内的趋化因子信号通路与巨噬细胞的相互作用最为密切。结论:我们的研究细化了晚期NSCLC中TAN亚型,并绘制了TAN在单细胞分辨率下的转录组图谱,共同表明了NSCLC中TAN的异质性。研究还发现了中性粒细胞分化和成熟相关基因,揭示了TAN亚克隆在肿瘤免疫逃逸中的不同功能,并可能进一步为免疫治疗提供新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.

Purpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.

Materials and methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.

Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.

Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
8.10
自引率
0.00%
发文量
10
审稿时长
16 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信