晚期卵巢癌患者一线化疗后机体免疫重建的动态研究

目的:研究晚期卵巢癌患者一线化疗后免疫细胞数量和表型的动态变化, 探询化疗后机体是否存在免疫重建的动态过程, 为制定化疗联合免疫治疗方案提供实验依据.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, 采集化疗前(S0)、化疗后5~7 d(S1)、化疗后12~14 d(S2)和化疗后25~28 d(S3)外周血, 流式细胞术检测患者外周血中CD3+、 CD4+、 CD8+细胞、 CD4+CD25+ Treg细胞的百分比及绝对数量, 并进一步分析CD4+和CD8+细胞中记忆细胞、原始细胞的比例.结果:在一个完整的化疗周期中, 淋巴细胞的总数量在化疗后S1期下降至最低, S2期即开始恢复, 到S3期则已恢复到化疗前水平;CD3+、 CD4+、 CD8+细胞及CD4+CD25+ Treg细胞的绝对数目均于S1期降至最低点, 且与S0期分别都有统计学差异;CD8+细胞的比例于S1期降至最低;CD4+CD25+ Treg细胞的比例于S2期降至最低;CD4+CD45RO+和CD8+CD45RO+细胞的比例于S2期升至最高, 而CD8+CD45RA+细胞的比例于S2期最低.结论:紫杉醇联合卡铂诱发卵巢癌患者于化疗后5~7 d出现一过性淋巴细胞减少症, 之后开始产生淋巴细胞自稳性增生(免疫重建).免疫重建期可能是免疫治疗实施的最佳窗口期.

Immune reconstitution in advanced ovarian cancer patients undergoing first line chemotherapy

AIM: We investigated the numbers and proportions of lymphocyte subsets in advanced ovarian cancer patients undergoing chemotherapy, so as to identify whether there is immune reconstitution after chemotherapy, and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. METHODS: Blood samples from each ovarian cancer patient were obtained before (S_0) and at day 5-7 (S_1), day 12-14 (S_2) and day 25-28 (S_3) after chemotherapy in 13 patients. Flow cytometry technique was employed to analyse the numbers, proportions of CD3~+, CD4~+, CD8~+, CD4~+CD25~+ Treg and memory-like phenotype lymphocyte subsets. RESULTS: Lymphopenia was observed at S1 after chemotherapy, but lymphocytes were found gradually recovered after S1. The numbers of CD3~+, CD4~+, CD8~+T cells and CD4~+CD25~+ Treg cells reduced to the lowest on S_1. The proportions of CD8~+ T cells and CD4~+CD25~+ Treg cells reduced to the lowest on S_1 and S_2 respectively. The proportions of CD45RO~+ memory T cells increased significantly on S2 while the proportion of CD8~+CD45RA~+ T cells decreased remarkably on S_2. CONCLUSION: Paclitaxel and carboplatin induce lymphopenia at day 5-7 after chemotherapy, then comes the temporary immune reconstitution. It probably turns out that the "window period" during immune reconstitution offers a best opportunity for cancer immunotherapy.