北京中医药大学学报2026，Vol.49Issue(1)：38-48,11.DOI:10.3969/j.issn.1006-2157.2026.01.006
表没食子儿茶素没食子酸酯诱导巨噬细胞极化增强抗肿瘤免疫反应的机制研究
Mechanism of epigallocatechin-3-gallate-induced macrophage polarisation and enhance anti-tumor immune response
摘要
Abstract
Objective Objective To investigate the mechanism by which epigallocatechin gallate(EGCG)induces macrophage polarisation via the stimulator of interferon genes(STING)signalling pathway.Methods A Lewis lung carcinoma transplanted tumor mouse model was established using SPF-grade 6-8-week-old male C57BL/6 mice.Twenty-four successfully established mice were randomly assigned using a random number table to the control group,EGCG group,and cisplatin(DDP)group,with eight mice per group.Administration commenced when subcutaneous tumor volume reached approximately 80 mm3.The EGCG group received intraperitoneal injections of 50 mg/kg EGCG solution daily;the DDP group received 2 mg/kg DDP solution intraperitoneally three times weekly;the control group received intraperitoneal injections of saline solution of identical formulation and volume daily.Treatment continued for 14 consecutive days.General condition and body weight changes were monitored,alongside tumor volume alterations and tumor suppression rates across groups.Hematoxylin-eosin staining was used to examine cardiac,hepatic,and renal alterations in each group.Flow cytometry assessed the expression of marker molecules and the proportion of immune cells reflecting classical activated(M1)versus alternative activated(M2)macrophage polarisation in tumor-associated macrophages(TAMs)within tumor tissues.Immunofluorescence was employed to detect changes in tumor-associated macrophage phenotypes within tumor tissues,whilst Western blotting assessed STING signalling pathway protein expression.Results No significant changes in body weight were observed across groups during the treatment period.Compared to the control group,both the EGCG and DDP groups significantly inhibited tumor growth in mice(P<0.01),with favourable safety profiles in major organs.Flow cytometry revealed that,relative to the control group,the EGCG group exhibited a reduced proportion of cells positive for CD206,a characteristic surface marker of M2 macrophages(P<0.01),while expression of CD86,a specific marker for M1 TAMs,was elevated(P<0.05).The DDP group also demonstrated a reduced proportion of CD206-positive cells(P<0.05).Changes in the immune microenvironment:Compared with the control group,the EGCG group exhibited increased infiltration of CD8+T cells and dendritic cells(DCs)in tumor tissue(P<0.05),alongside reduced proportions of regulatory T cells(Tregs)and myeloid-derived suppressor cells(MDSCs)(P<0.05).The DDP group demonstrated increased DC proportion and reduced Treg and MDSC proportions(P<0.05).Immunofluorescence analysis revealed reduced CD206 expression and increased CD86 expression in both the EGCG and DDP groups compared with the control group(P<0.05,P<0.01);Western blot analysis revealed that,compared with the control group,the EGCG group exhibited increased protein expression of STING,TANK-binding kinase 1(TBK1),phosphorylated TBK1,interferon-regulated factor 3(IRF3),and phosphorylated IRF3(P<0.05,P<0.01),while the DDP group showed increased STING protein expression(P<0.05).Conclusion EGCG promotes the polarisation of TAMs from M2 to M1 type by activating the STING signalling pathway,thereby remodelling the immunosuppressive microenvironment in non-small cell lung cancer and enhancing the anti-tumor immune response.关键词
非小细胞肺癌/表没食子儿茶素没食子酸酯/巨噬细胞极化/免疫微环境/小鼠Key words
non-small cell lung cancer/epigallocatechin-3-gallate/macrophage polarisation/tumor immune microenvironment/mice分类
医药卫生引用本文复制引用
杨茜茹,李光达,卢泰成,张敬芝,李天翔,张宇,王婧,侯丽..表没食子儿茶素没食子酸酯诱导巨噬细胞极化增强抗肿瘤免疫反应的机制研究[J].北京中医药大学学报,2026,49(1):38-48,11.基金项目
国家自然科学基金项目(No.82172760) （No.82172760）
中央高水平中医医院临床科研业务费资助项目(No.CZ015) National Natural Science Foundation of China(No.82172760) （No.CZ015）
