Natural killer cell activity depression in peripheral blood and ascites from gastric cancer patients with high TGF-β1 expression

Abstract

Transforming growth factor beta(1) (TGF-beta(1)) has been shown to inhibit the function of various types of cells in vitro such as natural killer (NK) cells. However; this activity has not been well characterized in vivo. Therefore, twenty three patients with advanced gastric adenocarcinoma (AGC), with cytologically-proven malignant ascites, were evaluated in this study. We determined whether the NK activities of their lymphocytes from either peripheral blood or ascites were suppressed by tumor cell TGF-beta(1) expression. We also examined whether NK activity was more suppressed in peripheral blood versus in ascites where tumor cell-derived TGF-beta(1) is potentially more locally concentrated. The expression of TGF-beta(1) mRNA was examined in the armor cells from the ascitic fluid of the AGC patients. The NK activities of lymphocytes in peripheral blood and ascites were measured by the 4-hour Cr-51-release assay. We determined that eleven of twenty three patients had armor cells expressing high levels of TGF-beta(1) mRNA. The NK activity in these eleven patients was significantly lower than the NK activity in peripheral blood and ascites from twelve patients with low TGF-beta(1) expression. In addition, the NK activity in malignant ascites was significantly lower than the activity in peripheral blood in these high TGF-beta(1)-expressing cancer patients (p<0.05). We also monitored survival time in these advanced gastric cancer patients. However, the patients with high expression of TGF-beta(1) showed a trend towards reduced survival although this was not statistically significant. The data in this study are consistent with observations in the previous experiments that showed inhibitory effects of TGF-beta(1) on NK activities in vitro, we reported the same phenomenon in patients with advanced gastric cancer.