Increased apoptosis and elevated Fas expression in circulating natural killer cells in gastric cancer patients

Abstract

Background: Immune cells undergo extensive apoptosis in patients with cancer, which may be related to immune evasion by cancerous cells. The present study was designed to investigate the relationship between natural killer (NK) cell apoptosis and Fas expression in gastric cancer patients. Methods: NK cell apoptosis and Fas expression were evaluated by multicolor flow cytometry. Soluble Fas ligand (sFasL) was quantitated by enzyme-linked immunosorbent assay. Results: The frequency of apoptotic NK cells in gastric cancer patients was significantly higher than in normal controls (p = 0.0016). Moreover, their frequency was related to the progression of gastric cancer. Fas-positive NK cells were significantly more common in gastric cancer patients compared with normal controls (p = 0.034). Furthermore, Fas expression was closely related to the frequency of NK cell apoptosis (r = 0.6, p < 0.0001). The frequency of tumor-infiltrating NK cell apoptosis was significantly higher than that of circulating NK cell apoptosis (p = 0.035). Furthermore, Fas-positive NK cells in gastric cancer tissues occurred significantly more often than in peripheral blood (p = 0.029). FasL concentration in gastric cancer patients was lower than that in normal controls, and the difference tended to be significant (p = 0.057). Apoptotic circulating NK cells significantly decreased after surgery compared to before surgery (p = 0.023). Furthermore, Fas expression on circulating NK cells also significantly decreased after surgery compared with before surgery (p = 0.021). Conclusions: Upregulation of Fas expression on NK cells is related to increased apoptosis of circulating NK cells in gastric cancer patients. © 2012 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.