放疗联合抑制STAT3表达对肿瘤浸润树突状细胞成熟的影响

Combining Radiotherapy with STAT3 Silencing Promotes the Maturation of Tumor-infiltrating Dendritic Cell

目的:研究放疗联合抑制信号转导与转录激活因子3(STAT3)表达对肿瘤浸润树突状细胞(TIDCs)成熟的影响。方法:在BALB/c小鼠大腿皮下接种小鼠恶性B细胞淋巴瘤A20细胞形成肿瘤,在肿瘤内注射STAT3基因特异的shRNA质粒并进行放疗;从肿瘤中富集TIDCs,采用荧光定量聚合酶链式反应(q PCR)方法检测TIDCs中STAT3 mRNA表达水平,蛋白染色方法检测磷酸化STAT3蛋白表达水平和DCs表面分子MHCII、CD40及CD80的表达,用流式细胞仪收集细胞染色数据。结果:放疗联合抑制STAT3表达显著降低肿瘤浸润TIDCs中STAT3 mRNA表达水平和STAT3蛋白磷酸化水平;与单独放疗相比,放疗联合抑制STAT3表达显著增加肿瘤浸润TIDCs表面分子MHCII、CD40、CD80及CD86的表达水平。结论:放疗联合抑制STAT3治疗表达能促进肿瘤浸润TIDCs的成熟。

Objective： To investigate the effect of combination of radiotherapy with STAT3 silencing on the maturation of tumor-infiltrating dendritic cells. Methods： Murine malignant B cell cell lymphoma A20 cells were subcetaneously implanted in BALB / c mice to grow tumors. Tumors were treated with a plasmid expressing STAT3-specific shRNA by intratumor injection and local radiation. Tumorinfiltrating dendritic cells（ TIDCs） were enriched from tumors. STAT3 mRNA level in TIDCs was determined by q PRC,phospho-STAT3 level by intracellular staining and subsequent data collected by flow cytometry. The expression of MHCII,CD40,CD80 and CD86 were determined by extracellular staining and subsequent data collected by flow cytometry. Results： Combination of radiotherapy with STAT3 silencing inhibited STAT3 mRNA and decreased phosphorylation level of STAT3. Compared to radiotherapy alone,STAT3 silencing plus radiotherapy significantly upregulated the expression of MHCII,CD40 and CD80. Conclusions： Radiotherapy combined STAT3 inhibition promotes the maturation of tumor-infiltrating dendritic cells.