【摘 要】
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The chemokine receptor CCR4 is preferentially expressed on certain immune cells and some haematological tumor cells,which play pivotal roles in suppression of host immune response.However,the reasons
【机 构】
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Department of Clinical Laboratory,Qilu Hospital,Shandong University,Jinan,Shandong,China 250012
【出 处】
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第三次全国中西医结合检验医学学术会议
论文部分内容阅读
The chemokine receptor CCR4 is preferentially expressed on certain immune cells and some haematological tumor cells,which play pivotal roles in suppression of host immune response.However,the reasons for the up-modulation of CCR4 and its immune functions in solid tumors remain unclear.Herein,we aimed to determine the expression profiles of CCR4 in gastric cancer cells and its role in regulating anti-tumor immunity.CCR4 expression was assessed in 63 cases of gastric cancinomas by immunohistochemistry.We found cancer cells in lymphocyte-rich carcinomas more frequently showed moderate to strong positive staining for CCR4 than those in conventional carcinomas(P=0.041),and also found a positive relationship between expression of CCR4 and tumor necrosis factor-alpha(P=0.012).Stimulation of gastric cell lines with various cytokines showed that tumor necrosis factor-alpha uniquely up-modulated CCR4 expression via activation of nuclear factor kappa B.Additional coculture experiments showed the forced expression of CCR4 in SGC-7901 cells caused a significant reduction of interferon-gamma and elevation of interleukin-10 secretion in the supernatants from co-cultured SGC-7901 cells and peripheral blood mononuclear cells; meanwhile,granzyme A production in cancer cell-cocultured CD56+natural killer cells was significantly down-regulated.Inhibition of the overexpressed CCR4 in cancer cells by an inhibitor of CCR4,compound 39,proved to partly restore the antitumor immunity in respect of the inverse changes in those factors.Our studies suggest that the aberrant expression of CCR4 in human gastric cancer may contribute to tumor-induced immunosuppression.Conceivably,down-modulation of CCR4 expression may be a promising immunotherapy for human gastric cancer.
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