中国病理生理杂志2025，Vol.41Issue(5)：851-860,10.DOI:10.3969/j.issn.1000-4718.2025.05.003
M2-TAMs源性TGF-β1抑制CD8+T细胞免疫功能并促进食管癌进展
M2-TAMs-derived TGF-β1 inhibits CD8+T cell immune function and pro-motes progression of esophageal cancer
摘要
Abstract
AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.关键词
食管癌/肿瘤微环境/M2样肿瘤相关巨噬细胞/CD8+T细胞/转化生长因子β1Key words
esophageal carcinoma/tumor microenvironment/M2-like tumor-associated macrophages/CD8+T cells/transforming growth factor-β1分类
基础医学引用本文复制引用
陈素芳,胡建明,任祎琳,杨凯歌,井玉莹,陈凯,段余钡,罗成华,王良海,杨兰..M2-TAMs源性TGF-β1抑制CD8+T细胞免疫功能并促进食管癌进展[J].中国病理生理杂志,2025,41(5):851-860,10.基金项目
国家自然科学基金资助项目(No.82460597) （No.82460597）
兵团重点领域科技攻关项目(No.2023AB058) （No.2023AB058）
兵团指导性科技计划项目(No.2022ZD003 （）
No.2023ZD027 （）
No.2023ZD028) （）
石河子大学基础研究计划项目(No.MSPY202407) （No.MSPY202407）
