An oligonucleotide decoy for Stat3 activates the immune response of macrophages to breast cancer.
Tumor-associated macrophages (TAMs) have the potential to induce both immune activation and immune tolerance. Recent studies have indicated that in breast cancers the pro-tumor role of TAMs is dominant. We induced rat peritoneal macrophages with rat breast cancer cell-conditioned medium and analyzed signal transducer and activators of transcription 3 (Stat3) activities of the cells. Then these cells were transfected with Stat3 decoy oligonucleotides (ODNs) and were stimulated by lipopolysaccharide (LPS). The results demonstrate that induced macrophages displayed a reduction of cytotoxicity and antigen-presenting function in comparison with control but transfection with Stat3 decoy ODNs enhanced cytotoxicity and antigen-presenting function of the macrophages. Furthermore, injection of induced macrophages promoted tumor growth accompanied by immunosuppression in the rat tumor models, but injection of induced macrophages transfected with Stat3 decoy ODNs led to retarded tumor growth accompanied by immune activation. The data suggest that immunosuppressive activities of TAMs correlate with over-activated Stat3 signaling of the cells and disruption of Stat3 activity of TAMs can enhance rat immune response to breast cancer.
Sun
Zhengkui
Z
Department of General Surgery, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400016, China. sunzhengkui616@163.com
Yao
Zhenxiang
Z
Liu
Shengchun
S
Tang
Hua
H
Yan
Xiong
X
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D001665:Binding Sites; D005260:Female; D016753:Interleukin-10 / Q000502:physiology; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; C494088:Stat3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10