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Natural killer cell activity depression in peripheral blood and ascites from gastric cancer patients with high
1Department of Internal Medicine, Seoul National University Hospital, Korea.
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 tumor 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 51Cr-release assay. We determined that eleven of twenty three patients had tumor 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.
Insights
Transforming growth factor beta 1 (TGF-beta 1) suppresses natural killer (NK) cell activity in advanced gastric cancer patients. This inhibition is more pronounced in malignant ascites compared to peripheral blood, correlating with tumor TGF-beta 1 expression.
Area of Science:
- Immunology
- Oncology
- Gastroenterology
Background:
- Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit natural killer (NK) cell function in vitro.
- Its in vivo activity, particularly in advanced gastric adenocarcinoma (AGC), remains less characterized.
Purpose of the Study:
- To investigate the in vivo effect of tumor cell-derived TGF-beta 1 on NK cell activity in patients with AGC.
- To compare NK cell activity in peripheral blood versus malignant ascites.
- To assess the correlation between TGF-beta 1 expression and NK cell function and patient survival.
Main Methods:
- Analysis of TGF-beta 1 mRNA expression in tumor cells from ascitic fluid of 23 AGC patients.
- Measurement of NK cell activity in peripheral blood and ascites using a 51Cr-release assay.
- Correlation of TGF-beta 1 levels with NK activity and survival data.
Main Results:
- Eleven of 23 patients exhibited high TGF-beta 1 mRNA expression in tumor cells.
- Significantly lower NK activity was observed in patients with high TGF-beta 1 expression compared to those with low expression.
- NK activity was significantly more suppressed in malignant ascites than in peripheral blood among patients with high TGF-beta 1 expression (p < 0.05).
Conclusions:
- Tumor-expressed TGF-beta 1 suppresses NK cell activity in vivo in advanced gastric cancer patients.
- Malignant ascites shows greater NK cell suppression than peripheral blood, likely due to local TGF-beta 1 concentration.
- These findings support the in vitro observations and highlight TGF-beta 1's role in immune evasion in gastric cancer.