Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
World J Gastroenterol. 2012 Apr 7;18(13):1470-8. doi: 10.3748/wjg.v18.i13.1470.
To investigate the immunological repertoire in the peritoneal cavity of gastric cancer patients.
The peritoneal cavity is a compartment in which immunological host-tumor interactions can occur. However, the role of lymphocytes in the peritoneal cavity of gastric cancer patients is unclear. We observed 64 patients who underwent gastrectomy for gastric cancer and 11 patients who underwent laparoscopic cholecystectomy for gallstones and acted as controls. Lymphocytes isolated from both peripheral blood and peritoneal lavage were analyzed for surface markers of lymphocytes and their cytokine production by flow cytometry. CD4(+)CD25(high) T cells isolated from the patient's peripheral blood were co-cultivated for 4 d with the intra-peritoneal lymphocytes, and a cytokine assay was performed.
At gastrectomy, CCR7(-) CD45RA(-) CD8(+) effector memory T cells were observed in the peritoneal cavity. The frequency of CD4(+) CD25 (high) T cells in both the peripheral blood and peritoneal cavity was elevated in patients at advanced stage [control vs stage IV in the peripheral blood: 6.89 (3.39-10.4) vs 15.34 (11.37-19.31), P < 0.05, control vs stage IV in the peritoneal cavity: 8.65 (5.28-12.0) vs 19.56 (14.81-24.32), P < 0.05]. On the other hand, the suppression was restored with CD4(+) CD25(high) T cells from their own peripheral blood. This study is the first to analyze lymphocyte and cytokine production in the peritoneal cavity in patients with gastric cancer. Immune regulation at advanced stage is reversible at the point of gastrectomy.
The immunological milieu in the peritoneal cavity of patients with advanced gastric cancer elicited a Th2 response even at gastrectomy, but this response was reversible.
研究胃癌患者腹腔内的免疫谱。
腹腔是免疫宿主-肿瘤相互作用发生的部位。然而,淋巴细胞在胃癌患者腹腔中的作用尚不清楚。我们观察了 64 例行胃癌根治术的患者和 11 例行腹腔镜胆囊切除术的患者(作为对照)。通过流式细胞术分析从外周血和腹腔灌洗液中分离的淋巴细胞的表面标记物及其细胞因子产生。从患者外周血中分离出的 CD4(+)CD25(high)T 细胞与腹腔内淋巴细胞共培养 4 天,并进行细胞因子检测。
在行胃癌根治术时,观察到腹腔内 CCR7(-)CD45RA(-)CD8(+)效应记忆 T 细胞。晚期患者外周血和腹腔中 CD4(+)CD25(high)T 细胞的频率升高[对照组与 IV 期患者外周血:6.89(3.39-10.4)与 15.34(11.37-19.31),P<0.05;对照组与 IV 期患者腹腔:8.65(5.28-12.0)与 19.56(14.81-24.32),P<0.05]。另一方面,通过来自自身外周血的 CD4(+)CD25(high)T 细胞恢复了抑制作用。本研究首次分析了胃癌患者腹腔内淋巴细胞和细胞因子的产生。晚期患者腹腔内的免疫调节在胃癌根治术时是可以逆转的。
即使在行胃癌根治术时,晚期胃癌患者腹腔内的免疫微环境也会引发 Th2 反应,但这种反应是可以逆转的。