目的研究晚期卵巢癌患者经一线化疗后体内Tc1/Tc2免疫细胞亚群漂移及免疫应答功能的动态变化,以期明确化疗后机体是否存在抗肿瘤免疫抑制暂时逆转的“窗口期”。方法选取术后行紫杉醇联合卡铂化疗的晚期卵巢上皮癌患者共13例为患者组,健康女性13例作为对照组。采集化疗前(S0)、化疗后5~7d(S1)、化疗后12~14d(S2)和化疗后25~28d(S3)外周血,流式细胞术检测患者外周血中Tc1/Tc2免疫细胞亚群的动态变化,同时采用体外自体肿瘤细胞裂解物脉冲淋巴细胞共培养的方法检测不同时间点CD8^+细胞IFN-γ的分泌功能。结果晚期卵巢癌患者化疗前Tc1比例、Tc1/Tc2细胞比值较对照组显著降低,而Tc2比例则显著升高。化疗后Tc1细胞比例在S2期较S0期显著增高,Tc2细胞比例在化疗后无显著变化,Tc1/Tc2细胞比值在S2期显著增高。当体外给予自身肿瘤细胞裂解物刺激诱导培养后,分泌IFN-γ的CD8^+细胞比例在S2期达到最高。结论卵巢癌患者于一线化疗后机体Tc1/Tc2亚群动态漂移,其细胞比值在S2期显著升高;S2期亦是CD8^+细胞免疫应答达到最高峰的时间点。化疗有可能通过机体免疫重建诱生了增强的抗肿瘤免疫应答,从而使机体抗肿瘤免疫抑制得到暂时逆转。免疫重建期可能是免疫治疗实施的最佳窗口期。
Objective To investigate the changes of Tc1/Tc2 profiles and the cytotoxic function of CD8^+ cells in ovarian cancer patients undergoing paclitaxel and carboplatin chemotherapy, so as to identify whether there is a "window period" of anti-tumor immune suppression reverse after chemotherapy. Methods Blood samples from each ovarian cancer patient were obtained before (S0 ) and at day 5-7 (S1 ), day 12-14 ( S2 ) and day 25-28 ( S3 ) after chemotherapy in 13 patients. Thirteen age-matched healthy female volunteers were enrolled as a control group. Flow cytometry technique was employed to analyze the proportion of Tc1/ Tc2. The numbers of specific IFN-γ/ secreting CD8^+ cells were also calculated after peripheral lymphocytes had been stimulated with self tumor lysates. Results The proportion of Tcl in CD8^+ cells increased remarkably on S2 while the proportion of Tc2 in CD8^+ cells remained no significant changes after chemotherapy. The ratio of Tcl to Tc2 cells reached the highest on S2. IFN-γ secreting CD8^+ T cells also increased remarkably on S2, especially when CD8^+ T cells were stimulated with autologous tumor antigen. Conclusion Paclitaxel and carboplatin induce the changes of Tc1/Tc2 profile and augment anti-tumor immune response by immune reconstitution. It probably turns out that the "window period" during immune reconstitution offers a best opportunity for cancer immunotherapy.