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目的:观察吉西他滨对荷B细胞淋巴瘤小鼠脾脏中髓源抑制性细胞(myeloid derived suppressor cell,MDSC)的影响,以及吉西他滨化疗联合树突状细胞(dendritic cells,DCs)治疗巨大淋巴瘤的疗效。方法:小鼠皮下接种A20淋巴瘤细胞,30 d后形成巨大肿瘤,流式细胞仪分析吉西他滨化疗前后荷瘤小鼠脾脏中Gr-1+CD11b+MDSC的比例,免疫磁珠纯化的脾脏MDSC体外加入吉西他滨共培养后,Annexin-V/PI标记法检测细胞凋亡;观察荷瘤小鼠接受吉西他滨化疗联合DCs瘤内注射后肿瘤生长情况及小鼠存活期。结果:荷A20淋巴瘤小鼠脾脏中MDSC的比例显著上调,是正常小鼠脾脏中的10倍以上。体外吉西他滨时间依赖性诱导MDSC凋亡与坏死;荷瘤小鼠体内注射吉西他滨后,脾脏中绝大部分的MDSC被清除。单独吉西他滨注射或DCs瘤内注射对肿瘤生长产生一定的抑制作用,小鼠平均存活天数分别为(48.8±3.6)d和(47.2±7.4)d,而对照组小鼠平均存活天数为(38.8±2.2)d;吉西他滨化疗联合DCs瘤内注射后瘤体持续显著缩小,60%小鼠存活时间均超过90 d。结论:吉西他滨可有效清除荷瘤小鼠脾脏MDSC,吉西他滨化疗与DCs瘤内注射免疫治疗具有协同效应,可以提高对巨大淋巴瘤的疗效,本实验为应用生物化疗综合治疗模式治疗复发、难治性淋巴瘤提供了实验依据。
AIM: To observe the effect of gemcitabine on myeloid derived suppressor cells (MDSCs) in spleen of mice with B-cell lymphoma and the effect of gemcitabine chemotherapy combined with dendritic cells (DCs) in treating giant lymphoma . Methods: A20 lymphoma cells were inoculated subcutaneously in mice. After 30 days, a large tumor was formed. The proportion of Gr-1 + CD11b + MDSC in spleen of tumor-bearing mice before and after gemcitabine chemotherapy was analyzed by flow cytometry. After co-cultured with gemcitabine, the cell apoptosis was detected by Annexin-V / PI labeling method. The tumor growth of mice bearing tumor treated with gemcitabine combined with DCs and the survival of mice were observed. Results: The percentage of MDSC in the spleen of A20 lymphoma mice was significantly up-regulated, which was more than 10 times that of normal mice. In vitro, gemcitabine induced apoptosis and necrosis of MDSCs in a time-dependent manner. Most of the MDSCs in the spleen were eliminated after injecting gemcitabine in tumor-bearing mice. Gemcitabine injection alone or intratumoral intratumoral injection of DCs had some effects on tumor growth. The average number of days of survival in mice was (48.8 ± 3.6) days and (47.2 ± 7.4) days respectively, while the average survival time in control mice was (38.8 ± 2.2) d. After the intratumoral injection of gemcitabine chemotherapy and DCs, the tumor size continued to decrease significantly, and 60% of the mice survived for more than 90 days. Conclusion: Gemcitabine can effectively clear the spleen MDSC of tumor-bearing mice, and the combination of gemcitabine chemotherapy and DC intratumoral injection immunotherapy has a synergistic effect, which can improve the curative effect on giant lymphoma. This experiment is to apply the biotherapy combined therapy model to treat relapse and refractory Lymphomas provide experimental evidence.