Tumor-derived TrxR1 promotes macrophage immunosuppression in breast cancer
10.16753/j.cnki.1008-2344.2025.02.010
- VernacularTitle:乳腺肿瘤来源TrxR1促进巨噬细胞免疫抑制性
- Author:
Siyu SUN
1
;
Song ZHANG
1
;
Yanyan WANG
1
;
Xuanhe LI
1
;
Fangqian JIANG
1
;
Tingjing YAO
1
Author Information
1. 蚌埠医科大学第一附属医院肿瘤外科,安徽 蚌埠 233004
- Publication Type:Journal Article
- Keywords:
breast cancer;
TrxR1;
tumor-associated macrophage;
microenvironment;
immunosuppression
- From:
Journal of Shenyang Medical College
2025;27(2):168-173
- CountryChina
- Language:Chinese
-
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.
