Aberrant expression of p-STAT3 in peripheral blood CD4(+) and CD8(+) T cells related to hepatocellular carcinoma development

作者：Wang, Xu; Xin, Wenbin; Zhang, Hua; Zhang, Fengmei; Gao, Meilan; Yuan, Lingling; Xu, Xiaoyan; Hu, Xuemei; Zhao, Mingdong^*

来源：Molecular Medicine Reports, 2014, 10(5): 2649-2656.

DOI：10.3892/mmr.2014.2510

• p-STAT3
• peripheral blood
• CD4(+) T cells
• CD8(+) T cells
• immune surveillance
• pathogenesis
• hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancer types worldwide. The signal transducer and activator of transcription 3 (STAT3) protein is a member of the STAT transcription factor family. Oncogenesis, invasion, and metastasis of HCC are associated with activation of STAT3. However, whether aberrant expression of phosphorylated STAT3 (p-STAT3) in peripheral CD4(+) and CD8(+) T cells relates to HCC pathogenesis remains unclear. In this study, the expression of p-STAT3 in CD4(+) and CD8(+) T cells, and the levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6 and IL-10 in the human hepatoma cell line Huh7 co-cultured with peripheral blood mononucleated cells (PBMCs) of healthy volunteers were measured. The correlations between p-STAT3 and IFN-gamma/IL-4, IFN-gamma, IL-4, IL-6 and IL-10 were then analyzed. Results showed that the p-STAT3 level is higher. in CD4(+) and CD8(+) T cells in the peripheral blood of HCC patients, and in PBMCs co-cultured with Huh7 cells compared to controls. The cytokine (IL-4, IL-6 and IL-10) levels were increased and the IFN-gamma level was decreased in the serum of HCC patients and in supernatants of PBMCs co-cultured with Huh7 cells. Correlation analyses demonstrated that the IFN-gamma/IL-4 ratio and the IFN-gamma level negatively correlate to the p-STAT3 level in CD4(+) and CD8(+) T cells in samples from patients and in cells cultured in vitro. By contrast, the levels of IL-4, IL-6 and IL-10 positively correlated to the p-STAT3 level. This study indicated that the expression of p-STAT3 is upregulated in peripheral CD4(+) and CD8(+) T cells of HCC patients, and which may result in abnormal immune surveillance and thereby, contribute to HCC pathogenesis..

• 出版日期2014-11
• 单位滨州医学院