肿瘤预防与治疗2025，Vol.38Issue(5)：349-359,11.DOI:10.3969/j.issn.1674-0904.2025.05.001
FXR通过促进M2型巨噬细胞分化促进NSCLC进展
FXR Promotes NSCLC Progression by Driving M2 TAM Differentiation
摘要
Abstract
Objective:This study aims to explore the effect of farnesoid X receptor(FXR)expression in tumor-associated macrophages(TAMs)on non-small cell lung cancer(NSCLC)and provide potential therapeutic targets for immunotherapy of NSCLC.Methods:A total of 98 tissue sections from patients with NSCLC were subjected to immunohistochemistry staining for CD68 and FXR.The staining was then scored and graded for statistical correlation analysis.Additionally,bone marrow-derived stem cells from mice were extracted and differentiated into M0,M1,and M2 TAMs to assess the expression levels of FXR among these subtypes.After inhibiting the expression of FXR in M2 TAMs,the phenotypic alterations of TAMs were examined.Additionally,M2 TAMs were co-cultured with NSCLC cells to assess the changes in TAM phagocytic capacity and cancer cell proliferation,migration,and invasion capabil-ities.Results:In clinical samples from patients with NSCLC,a positive correlation was identified between the expression levels of FXR and CD68,with patients with FXRhigh-CD68high showing a poorer prognosis.Notably,FXR expres-sion was found to be highest in M2 TAMs,as compared to M0 and M1 subtypes.Inhibition of FXR significantly reduced the differentiation of M2 TAMs and markedly enhanced their phagocytic capacity against NSCLC cells,while concurrently decrea-sing the proliferation,migration,and invasion of co-cultured NSCLC cells.Conclusion:This study suggests that FXR plays a significant role in promoting the differentiation of M2 TAMs,thereby supporting their tumor-promoting functions in NSCLC.The expression of FXR in M2 TAMs may serve as a potential target for immunotherapy in NSCLC.关键词
肿瘤相关巨噬细胞/法尼酯X受体/非小细胞肺癌/肿瘤微环境Key words
Tumor-associated macrophages/Farnesoid X receptor/Non-small cell lung cancer/Tumor microenvironment分类
医药卫生引用本文复制引用
吴汉城,姚瑞霖,刘静,邵杨,游文杰..FXR通过促进M2型巨噬细胞分化促进NSCLC进展[J].肿瘤预防与治疗,2025,38(5):349-359,11.基金项目
This study was supported by grants from China Postdoctoral Science Foundation(No.2023M740684)and Jinan Municipal Bureau of Science and Technology(No.202225051). 中国博士后科学基金面上项目(编号:2023M740684) （No.2023M740684）
济南市科技发展计划项目(编号:202225051) （编号:202225051）
