Immuno-suppression and mechanism of CD4+CD25+T cells in ascites of ovarian cancer patients / 中国肿瘤临床

ABSTRACT

Objective: This research explores the relationship between the immuno-suppression function of regulatory T cells (Treg) in the ascites of ovarian cancer (OC) patients, the clinico-pathologic features of these patients, and the correlation of the function of Treg with initial treatment and relapse status of the patients to further investigate the specific mechanism of immuno-regulatory func-tion of CD4+ CD25+ Treg in the ascites of OC. Methods: Immuno-magnetic activated cell sorting (MACS) was conducted to sort CD4+CD25+Treg and autologous CD4+CD25-Treg from the ascites of 28 OC patients. Carboxyfluorescein-diacetate succinimidyl ester (CFSE) was used to label the autologous CD4+CD25-Treg. These labeled cells were then used as controls and co-cultured with autologous CD4+CD25+Treg at the ratio of 1∶1 or 1∶2. The mean inhibition ratio of Treg in specimens to the proliferation of autolo-gous CD4+ CD25-Treg was calculated after the flow cytometry of the CFSE expression and Modfit software analysis of the CD4+CD25-Treg proliferation index (PI) were performed. Anti-IL-10 and/or anti-TGF-β1 antibodies were neutralized to investigate whether the CD4+CD25+Treg-mediated immuno-suppression escaped through the ascites can produce a marked effect by the inhibitory cyto-kine IL-10 or TGF-β1. Results: The mean inhibition ratio of CD4+ CD25- Treg in the ascites of stage Ⅲ to Ⅳ OC patients was (75.72±17.04)%, which is significantly higher than that of stageⅠtoⅡOC patients (59.61±16.97)%;P<0.05. In addition, Treg in the as-cites of OC patients with recurrent disease showed a significantly higher inhibition ratio than that of patients with primary disease;P<0.001. Moreover, Treg in groups added into neutralizing anti-IL-10 and/or anti-TGF-β1 antibodies displayed significantly lower depres-sant effect than the control group;P<0.05. Conclusion:The immuno-suppression of CD4+CD25+Treg in the ascites of OC patients is correlated with the tumor staging and status of the primary or recurrent diseases. Moreover, Treg may indicate a suppressor function by secreting cytokine IL-10 and TGF-β1.