摘要目的 紫杉醇联合卡铂治疗鼠源性卵巢癌后,在免疫功能改变的不同时期给予冻融抗原疫苗免疫治疗,以寻求化疗联合疫苗治疗的最佳契机.方法 以荷瘤大鼠为研究对象,根据紫杉醇联合卡铂对荷瘤鼠免疫功能改变的不同时期分为6组:即未治疗组、化疗组、疫苗组、化疗后6 d+疫苗组、化疗后10 d+疫苗组、化疗后15 d+疫苗组,化疗后不同时期给予冻融抗原疫苗主动免疫治疗,观察荷瘤体积及机体免疫功能改变.结果 未治疗组鼠瘤体生长最迅速,而单纯疫苗组治疗组较平缓,其中化疗后第6天即淋巴细胞数量最少期给予免疫治疗肿瘤生长最缓慢;CT扫描结果显示,所有治疗组瘤体积较未治疗组体积均小且有差异;化疗后6 d+疫苗组瘤体积最小且与其余治疗组差异有统计学意义;荷瘤鼠免疫功能显示:化疗后6 d+疫苗组淋巴细胞抗原特异性增殖最为明显;CD8+T细胞数量在化疗后6 d联合免疫治疗组中增高且与其余治疗组有显著性差别;而Tr细胞在化疗后6 d+疫苗组明显降低,较其余组间差异有统计学意义;具有分泌IFN-γ杀伤功能的细胞在化疗后6 d+疫苗组最高.结论 紫杉醇+卡铂联合冻融抗原疫苗治疗卵巢癌具有协同作用,但这种协同作用与化疗后引起免疫功能变化有关,化疗后6 d为主动免疫治疗的最佳时间点;化疗造成的肿瘤个体免疫功能的低下或免疫系统空间的释放(所谓的免疫"窗口期"),为诱导特异性的抗肿瘤免疫应答提供了可能.

abstractsObjective To explore immunotherapy effective combined with active immunotherapy in different time according rats bearing-tumor after paclitaxel and carboplatin chemotherapy, and to identify the optimization time and strategy of vaccine and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. Methods The dynamic immunocytes number and function in established tumor treated with paclitaxel and carboplatin chemotherapy were investigated. The changes of established tumor volume and immune function of different groups were observed according to combining different time after chemotherapy and vaccine. Results Lymphopenia was observed and the number of lymphocyte subset decreased remarkably on the 6th day, but all cells were found almost recovered on 15th day after chemotherapy. There is the process of immune-enhancing from post-chemotherapy 6 day to 10 day and reversal of immune suppression temporary. The combination post-chemotherapy 6 day with CTL caused a significantly delayed tumor growth in both tumor models and induced significant the proliferation of T lymphocyte by [H] 3 releasing. The number of CD8+T cell is the highest, but the expression of Tr cell was lowest in the group of post-chemotherapy 6 day with CTL. Furthermore, the ability of CD8+T secretion IFN-γ is the most in the post-chemotherapy 6 day with immunotherapy groups. Conclusion Combinational paclitaxel and carboplatin chemotherapy has synergistic effects with active immunotherapy boosting against tumor during window periods, where 6 days after chemotherapy with the most decreased number of lymphocytes in the animal periphery might represent the optimal checkpoint for the immune therapy against tumors. Therefore, monitoring the immune status of tumor patients might become one of the important prerequisites for the effective immune therapy when designing the comprehensive therapeutic strategies.