DC-CIK细胞免疫治疗对卵巢癌患者免疫功能影响的研究

发布时间：2018-12-14 14:34

【摘要】：目的：卵巢癌是最常见的妇科恶性肿瘤，其发病率和死亡率居妇科恶性肿瘤之首，5年生存率仅为30%~40%。过继细胞免疫治疗越来越成为卵巢癌治疗的重要武器，本研究通过观察DC-CIK(dendriticcell-cytokineinducedkillercell)过继细胞免疫治疗对卵巢癌患者外周血淋巴细胞亚群及相关细胞因子的变化，评价DC-CIK细胞免疫治疗对卵巢癌临床疗效。方法：选取2010年3月至2013年3月在吉林大学第二医院肿瘤生物治疗中心治疗的22例卵巢癌患者，有明确的组织病理学检查。取外周血分离单个核细胞(PBMC)，在体外诱导出DC和CIK细胞，分别行7个周期的DC-CIK细胞免疫治疗，采用流式细胞术和酶联免疫法检测接受DC-CIK免疫治疗不同周期后，，其外周血中淋巴细胞亚群（包括T淋巴细胞亚群（CD3+）、辅助性T细胞亚群（CD3+/CD4+）、杀伤性T细胞亚群（CD3+/CD8+）、NKT细胞亚群（CD3+/CD16+56+）等）的变化，及相关因子白介素-2、肿瘤坏死因子-α、干扰素-γ的表达水平。同时对变态反应、血液系统、心血管系统、肝脏、肾脏、胃肠道、全身症状等进行监测，并进行安全性评价。利用SPSS13.0软件包进行数据的分析和处理。结果： 1.与治疗前相比，4周期及7个周期DC-CIK细胞免疫治疗组患者外周血T淋巴细胞亚群无显著变化，即T淋巴细胞亚群（CD3+）、辅助性T细胞亚群（CD3+/CD4+）、杀伤性T细胞亚群（CD3+/CD8+）、NKT细胞亚群（CD3+/CD16+56+）等与治疗前相比略有升高，但无显著统计学差异（P0.05）。 2.4周期治疗后，患者外周血白介素-2、肿瘤坏死因子-α、干扰素-γ水平较治疗前提高，但差异并不显著（P0.05），而当7个周期治疗后，IL-2、TNF-α、IFN-γ水平较治疗前明显提高且具有统计学差异（P0.05）； 3.DC-CIK过继性细胞免疫治疗后，患者躯体功能、情绪方面较治疗前改善明显。 4.患者显示出良好的耐受性，共计154周期的治疗中，不良反应发生率较低，发热，荨麻疹，心慌，肝脏损害均为一过性。结论： 1.DC-CIK细胞免疫治疗可以明显提高卵巢癌患者免疫状态，提高机体抗肿瘤能力，机体免疫力提升，生活质量显著提高。 2.临床应用无明显不良反应,是卵巢癌患者重要的辅助治疗手段。
[Abstract]:Objective: ovarian cancer is the most common gynecologic malignant tumor, its morbidity and mortality are the first among gynecological malignancies, and the 5-year survival rate is only 30%. Adoptive cellular immunotherapy has become an important weapon in ovarian cancer treatment. The changes of lymphocyte subsets and related cytokines in peripheral blood of patients with ovarian cancer were observed by DC-CIK (dendriticcell-cytokineinducedkillercell) adoptive cellular immunotherapy. To evaluate the clinical effect of DC-CIK cell immunotherapy on ovarian cancer. Methods: from March 2010 to March 2013, 22 patients with ovarian cancer treated in tumor biotherapy center of the second Hospital of Jilin University were examined by histopathological examination. DC and CIK cells were induced from peripheral blood mononuclear cells (PBMC),) in vitro and were treated with 7 cycles of DC-CIK cell immunotherapy respectively. Flow cytometry and enzyme-linked immunosorbent assay (Elisa) were used to detect the different cycles of DC-CIK immunotherapy. The changes of lymphocyte subsets (including T lymphocyte subsets (CD3), helper T cell subsets (CD3 / CD4), CD3 / CD8), NKT cell subsets (CD3 / CD16 56) in peripheral blood. The expression level of Interleukin-2, tumor necrosis factor-伪 and interferon-纬. Allergy, blood system, cardiovascular system, liver, kidney, gastrointestinal tract, systemic symptoms were monitored and safety was evaluated. SPSS13.0 software package is used to analyze and process the data. Results: 1. There were no significant changes in peripheral blood T lymphocyte subsets (CD3), helper T cell subsets (CD3 / CD4) in patients with 4 cycles and 7 cycles of DC-CIK cell immunotherapy compared with those before treatment. The lethal T cell subsets (CD3 / CD8), NKT cell subsets) (CD3 / CD16 56) were slightly higher than those before treatment, but there was no significant difference (P0.05). The levels of interleukin-2, tumor necrosis factor- 伪 and interferon- 纬 in peripheral blood were increased after 2. 4 cycles treatment, but the difference was not significant (P0.05). However, after 7 cycles of treatment, the levels of IL-2,TNF- 伪, TNF- 伪 and IFN- 纬 in peripheral blood of the patients were significantly higher than those before treatment (P0.05). The level of IFN- 纬 was significantly higher than that before treatment (P0.05). After adoptive cellular immunotherapy with 3.DC-CIK, the somatic function and mood of the patients improved significantly. 4. In 154 cycles of treatment, the incidence of adverse reactions was low, fever, urticaria, palpitation, and liver damage were transient. Conclusion: 1.DC-CIK cell immunotherapy can significantly improve the immune status of patients with ovarian cancer, improve the ability of anti-tumor, enhance the immunity of the body, and improve the quality of life. 2. There is no obvious adverse reaction in clinical application and it is an important adjuvant therapy for ovarian cancer patients.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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