Division of Surgical Oncology, Department of Surgery, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago, 683-8504, Japan,
Gastric Cancer. 2013 Oct;16(4):473-9. doi: 10.1007/s10120-012-0210-1. Epub 2012 Nov 22.
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.
NK cell apoptosis and Fas expression were evaluated by multicolor flow cytometry. Soluble Fas ligand (sFasL) was quantitated by enzyme-linked immunosorbent assay.
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).
Upregulation of Fas expression on NK cells is related to increased apoptosis of circulating NK cells in gastric cancer patients.
癌症患者的免疫细胞会发生广泛的凋亡，这可能与癌细胞的免疫逃逸有关。本研究旨在探讨胃癌患者自然杀伤（NK）细胞凋亡与 Fas 表达的关系。
采用多色流式细胞术检测 NK 细胞凋亡和 Fas 表达，酶联免疫吸附试验定量检测可溶性 Fas 配体（sFasL）。
胃癌患者凋亡 NK 细胞的频率明显高于正常对照组（p = 0.0016）。此外，其频率与胃癌的进展有关。与正常对照组相比，胃癌患者 Fas 阳性 NK 细胞更为常见（p = 0.034）。此外，Fas 表达与 NK 细胞凋亡频率密切相关（r = 0.6，p < 0.0001）。肿瘤浸润 NK 细胞凋亡的频率明显高于循环 NK 细胞凋亡（p = 0.035）。此外，胃癌组织中 Fas 阳性 NK 细胞的频率明显高于外周血（p = 0.029）。胃癌患者 FasL 浓度低于正常对照组，差异有统计学意义（p = 0.057）。与术前相比，手术后循环 NK 细胞的凋亡明显减少（p = 0.023）。此外，手术后循环 NK 细胞 Fas 表达也明显低于术前（p = 0.021）。
胃癌患者循环 NK 细胞 Fas 表达上调与 NK 细胞凋亡增加有关。
