沈阳医学院学报2025，Vol.27Issue(2)：168-173,6.DOI:10.16753/j.cnki.1008-2344.2025.02.010
乳腺肿瘤来源TrxR1促进巨噬细胞免疫抑制性
Tumor-derived TrxR1 promotes macrophage immunosuppression in breast cancer
摘要
Abstract
Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.关键词
乳腺癌/TrxR1/肿瘤相关巨噬细胞/微环境/免疫抑制性Key words
breast cancer/TrxR1/tumor-associated macrophage/microenvironment/immunosuppression分类
基础医学引用本文复制引用
孙思雨,张松,王岩岩,李煊赫,姜芳倩,姚廷敬..乳腺肿瘤来源TrxR1促进巨噬细胞免疫抑制性[J].沈阳医学院学报,2025,27(2):168-173,6.基金项目
2022年度蚌埠医学院科技项目(No.2022byzd052) （No.2022byzd052）
2024年度安徽省高等学校科研计划项目(No.2024AH040190) （No.2024AH040190）
