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作 者:吴绮丽 李汉平 WU Qi-li;LI Han-ping(Medical Research Institute,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China;Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China)
机构地区:[1]医学研究中心,南方医科大学附属广东省人民医院(广东省医学科学院),广州510080 [2]广东省冠心病防治研究重点实验室,南方医科大学附属广东省人民医院(广东省医学科学院),广州510080
出 处:《循证医学》2024年第6期372-379,共8页The Journal of Evidence-Based Medicine
基 金:广东省医学科学技术研究基金项目(B2021367)。
摘 要:目的本研究旨在探究表皮生长因子受体19外显子缺失(epidermal growth factor receptor exon 19 deletion,EGFR 19del)肺腺癌肿瘤微环境的免疫景观,并聚焦中性粒细胞的特征和作用,为免疫治疗提供新的策略。方法利用EGFR 19del肿瘤组织单细胞数据分析细胞异质性、细胞间通讯、配体-受体相互作用以及中性粒细胞相关基因的功能富集分析。结果我们发现EGFR 19del肿瘤环境中细胞比例改变,中性粒细胞通过加强OSM-(OSMR-LIF)、趋化因子C-X-C基序配体1(C-X-C motif chemokine ligand 1,CXCL1)和趋化因子C-C基序配体18(chemokine(C–C motif)ligand 18,CCL18)等关键配体-受体相互作用参与炎症反应和细胞趋化。此外,中性粒细胞在固有免疫、细胞因子产生和模式识别受体活性中扮演关键角色,并在NOD样受体、趋化因子信号通路发挥作用。结论中性粒细胞可能通过调控炎症和免疫细胞趋化影响肿瘤微环境,在EGFR 19del肺腺癌的发展和治疗反应中起关键作用,为免疫治疗提供新靶点。Objective This study aims to investigate the immune landscape of the epidermal growth factor receptor exon 19 deletion(EGFR 19del)lung adenocarcinoma tumor microenvironment,focusing on the characteristics and roles of neutrophils to provide new strategies for immunotherapy.Methods Single-cell data from EGFR 19del tumor tissues were analyzed for cellular heterogeneity,intercellular communication,ligand-receptor interactions,and functional enrichment analysis of neutrophil-related genes.Results We found altered cell proportions in the EGFR 19del tumor environment,with neutrophils participating in inflammatory responses and cell chemotaxis through enhanced interactions of key ligand-receptor pairs such as OSM-(OSMR-LIF),C-X-C motif chemokine ligand 1(CXCL1),and chemokine(C–C motif)ligand 18(CCL18).Additionally,neutrophils play a key role in innate immunity,cytokine production,and pattern recognition receptor activity,and function in NOD-like receptor and chemokine signaling pathways.Conclusion Neutrophils may play a crucial role in the development and therapeutic response of EGFR 19del lung adenocarcinoma by regulating inflammation and immune cell chemotaxis,affecting the tumor microenvironment and providing new targets for immunotherapy.
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