糖酵解产物乳酸对M_(2)-肿瘤相关巨噬细胞亚群重塑作用的研究  

Effect of lactic acid on reshaping of M_(2)-TAM subsets

作　　者：崔熙娟[1] 乔莉娜[1] 单涛[2] 陈硕[2] 杨屹[2] 张迪[2] CUI Xijuan;QIAO Lina;SHAN Tao;CHEN Shuo;YANG Yi;ZHANG Di(Department of General Surgery,the First Affiliated Hospital of Medical College,Xi'an Jiaotong University,Shaanxi Xi'an 710061,China;Department of General Surgery,the Second Affiliated Hospital of Medical College,Xi'an Jiaotong University,Shaanxi Xi'an 710004,China)

机构地区：[1]西安交通大学第一附属医院普外科,陕西西安710061 [2]西安交通大学第二附属医院普外科,陕西西安710004

出　　处：《现代肿瘤医学》2022年第14期2504-2508,共5页Journal of Modern Oncology

基　　金：陕西省自然科学基础研究计划-重点项目(编号:S2020-JC-ZD-0093);陕西省科技新星基金(编号:2018KJXX-058);西安交通大学科技人才(骨干)基金[编号:RC(GG)201708]。

摘　　要：目的:研究糖酵解产物乳酸对巨噬细胞表型极化的影响。方法:我们选取人单核/巨噬细胞系THP-1,乳酸处理后采用RT-PCR、Western blot、免疫荧光染色激光共聚焦、ELISA等手段,观察指标:CD68、CD163变化;分泌因子:TNF-α、IFN-γ、IL-12、IL-10变化。结果:15 mmol/L浓度的乳酸可显著上调巨噬细胞M_(2)型标志分子CD163的表达(P<0.05),上调M_(2)-TAM分泌因子IFN-γ和IL-10的表达(P<0.05),下调M_(1)-TAM分泌因子TNF-α和IL-12的表达(P<0.05)。结论:乳酸可重塑巨噬细胞向M_(2)-TAM亚群分布,揭示肿瘤细胞糖酵解产生乳酸可能通过重塑巨噬细胞表型发挥重要的促瘤作用。Objective:To study the effects of lactic acid on phenotypic polarization of macrophages.Methods:The human monocyte/macrophage cell line THP-1 was selected and treated with lactic acid.Immunofluorescence staining,laser confocal microscopy,RT-PCR,Western blot,and ELISA methods were used to observe changes in CD68,CD163 and the cytokine TNF-α,IFN-γ,IL-12,IL-10.Results:Lactic acid at a concentration of 15 mmol/L significantly up-regulated the expression of the M_(2)-macrophage marker CD163(P<0.05),up-regulated the expression of the cytokines IFN-γand IL-10 secreted by M_(2)-TAM(P<0.05),down-regulated the expression of the cytokines TNF-αand IL-12 secreted by M_(1)-TAM(P<0.05).Conclusion:Lactic acid can reshape the distribution of M_(2)-TAM subsets to assist tumor immune escape,revealing that macrophages,as"checkpoints"in organisms,are bridges connecting immune state and tumor evolution,and can be used as a target in tumor treatment.

关 键 词：巨噬细胞 肿瘤微环境 乳酸 

分 类 号：R730.2[医药卫生—肿瘤]