Konjevic G, Radenkovic S, Srdic T, Jurisic V, Stamatovic Lj, Milovic M
Institute of Oncology and Radiology of Serbia, Department of Experimental Oncology, Belgrade, Serbia.
J BUON. 2011 Apr-Jun;16(2):219-26.
Impaired IFNγ production in peripheral blood lymphocytes (PBL) and their subsets reflects immunosuppression and inadequate antitumor immune response in cancer patients. Decreased function of natural killer (NK) cells has not been investigated in breast cancer with respect to altered pSTAT signaling pathways.
PBL of breast cancer patients and healthy controls were analyzed for IFNγ and pSTAT1 expression and NK cell activity using flow cytometry and (51)Cr-release assay, respectively. The level of pSTAT1, 3 and 5 was investigated by Western blotting.
Our results indicated that PBL and CD3(-) CD16(+) NK cells of patients had significantly lower level of IFNγ. The patients had a significantly decreased NK cell cytotoxicity compared to controls, with the decrease being dependent on the stage of disease. Positive correlation between IFNγ level in PBL and NK cytotoxicity in controls and patients was also shown. The PBL of patients, compared to controls, expressed lower level of pSTAT1, 3 and 5. The patients' T and NK cell subsets had lower pSTAT1 level.
This study indicates that pSTAT1 in PBL of breast cancer patients could be a biomarker of decreased NK cell cytotoxicity and IFNγlevel that are associated with progression of this disease.
外周血淋巴细胞（PBL）及其亚群中γ干扰素（IFNγ）产生受损反映了癌症患者的免疫抑制和抗肿瘤免疫反应不足。关于pSTAT信号通路改变，尚未在乳腺癌中研究自然杀伤（NK）细胞功能的降低情况。
分别使用流式细胞术和铬（51）释放试验分析乳腺癌患者和健康对照的PBL中IFNγ和pSTAT1表达以及NK细胞活性。通过蛋白质印迹法研究pSTAT1、3和5的水平。
我们的结果表明，患者的PBL和CD3（-）CD16（+）NK细胞中IFNγ水平显著降低。与对照组相比，患者的NK细胞细胞毒性显著降低，且这种降低取决于疾病阶段。还显示了对照组和患者中PBL中IFNγ水平与NK细胞毒性之间的正相关。与对照组相比，患者的PBL中pSTAT1、3和5的表达水平较低。患者的T细胞和NK细胞亚群中pSTAT1水平较低。
本研究表明，乳腺癌患者PBL中的pSTAT1可能是与该疾病进展相关的NK细胞细胞毒性降低和IFNγ水平降低的生物标志物。
