初诊肺癌患者多次化疗外周血免疫相关指标变化动态研究

发布时间：2018-06-15 15:05

本文选题：免疫治疗 + 淋巴细胞亚群　；参考：《新乡医学院》2017年硕士论文

【摘要】：背景肺癌已成为全世界范围内发病率和死亡率居首位的恶性肿瘤。随着分子免疫学的研究发展,免疫治疗日趋成为继手术、化疗、放疗之后的一种重要治疗手段。化疗与免疫治疗的结合,可以增强肿瘤抗原性、活化免疫功能,从而有效启动机体抗肿瘤免疫。然而,由于化疗药物对机体免疫功能的影响与药物种类、剂量、给药方式等密切相关,加之不同个体的免疫功能状态的差异性等等因素,将导致治疗过程中机体免疫功能状态复杂多变,化疗与免疫治疗的有利组合时机仍需探索。目的研究初诊肺癌患者多次化疗过程中,外周血淋巴细胞亚群数量、T淋巴细胞表面共信号分子、细胞因子等指标动态变化趋势,藉此观察治疗过程中机体免疫状态的变化趋势,评价患者全身免疫功能状况,多角度窥探化疗过程中机体错综复杂的免疫功能变化,探索免疫治疗与化疗结合的有利切入点,为临床免疫治疗介入提供实验依据。方法采用流式细胞术检测23例初诊肺癌患者5周期治疗前外周血中T淋巴细胞及其亚群数量、B淋巴细胞数量、NK细胞数量,T细胞表面共信号分子表达及细胞因子表达;收集患者临床资料及常规实验室检查数据。分析从第一周期到第五周期治疗过程中,上述指标变化趋势是否具有差异。应用Flowjo 7.6.1进行流式图分析,应用SPSS 20.0软件进行统计分析。所有计量数据均用（？）±s表示,两组间的比较采用独立样本t检验,P0.05为差异有统计学意义。结果1. 通过收集23例肺癌患者的资料,统计分析发现,多次化疗过程中外周血白细胞、中性粒细胞、淋巴细胞、血小板、血红蛋白的水平显著下降;2.患者血生化(总蛋白、白蛋白、球蛋白、谷丙转氨酶、谷草转氨酶、葡萄糖)指标变化不显著;3.CD8~+T淋巴细胞、CD19~+B淋巴细胞和CD16~+CD56~+NK细胞水平下调,CD4~+T淋巴细胞数量增加;4.CD8~+T淋巴细胞表面PD-1、CTLA-4和CCR-4表达上调,PD-L1表达水平下调,CD137整体表达无明显差异;5.CD4~+T淋巴细胞表面PD-1表达上调,PD-L1表达下调,CTLA-4、LAG-3、CCR-4和CD137表达整体变化不显著;6.外周血中细胞因子(IL-2、IFN-γ、IL-4、IL-6、IL-10、TNF-α和IL-17A)整体表达无显著差异。结论初诊肺癌患者多周期化疗过程中,机体CD8~+T淋巴细胞、CD19~+B淋巴细胞和CD16~+CD56~+NK细胞水平下调,CD4~+T淋巴细胞数量增加;T细胞表面共抑制分子PD-1、CTLA-4和CCR-4随治疗进行表达下调,监测上述指标变化对化疗联合免疫治疗综合治疗方案制定、预后评估具有重要意义。
[Abstract]:Background Lung cancer has become the world's leading morbidity and mortality of malignant tumors. With the development of molecular immunology, immunotherapy is becoming an important treatment after surgery, chemotherapy and radiotherapy. The combination of chemotherapy and immunotherapy can enhance the antigenicity of tumor, activate immune function, and effectively activate anti-tumor immunity. However, the influence of chemotherapeutic drugs on the immune function of the body is closely related to the kinds of drugs, the dosage, the way of administration, and the difference of the immune function of different individuals, and so on. It will lead to complex and changeable immune function in the course of treatment, and the favorable combination of chemotherapy and immunotherapy still needs to be explored. Objective to study the dynamic change trend of surface co-signal molecules and cytokines in peripheral blood lymphocyte subsets during multiple chemotherapy in newly diagnosed lung cancer patients, and to observe the change trend of immune status during treatment. To evaluate the systemic immune function of patients, to explore the complex changes of immune function in the course of multi-angle prying chemotherapy, to explore the beneficial breakthrough point of combination of immunotherapy and chemotherapy, and to provide experimental basis for the intervention of clinical immunotherapy. Methods flow cytometry was used to detect the number of T lymphocytes and its subsets in peripheral blood of 23 patients with lung cancer before 5-cycle treatment. The number of NK cells and the expression of co-signal molecules and cytokines on the surface of T cells were measured. Collect clinical data and routine laboratory data. To analyze whether the change trend of the above indexes is different from the first cycle to the fifth cycle. Flowjo 7.6.1 was used for flow chart analysis and SPSS 20.0 software for statistical analysis. All the measurement data were expressed in 卤s. The difference between the two groups was statistically significant by using independent sample t test (P0.05). Result 1. The data of 23 patients with lung cancer were collected. Statistical analysis showed that the levels of leukocytes, neutrophils, lymphocytes, platelets and hemoglobin in peripheral blood were significantly decreased during multiple chemotherapy. Patients' blood biochemistry (total protein, albumin, globulin, alanine aminotransferase, alanine aminotransferase, No significant changes of glucose were observed in CD8 ~ T lymphocytes, CD19 ~ B lymphocytes and CD16 ~ CD56 ~ NK cells. Increase in the number of CD4 ~ T lymphocytes on the surface of CD8 ~ T lymphocytes. Upregulation of PD-1CTLA-4 and CCR-4 expression down-regulates the whole expression of CD137 on the surface of CD8 ~ T lymphocytes. There was no significant difference in the expression of PD-1 on CD4 ~ T lymphocytes. The expression of PD-L1 down-regulated CTLA-4, LAG-3, CCR-4 and CD137 was not significantly changed. There was no significant difference in the expression of IL-10, TNF- 伪 and IL-17A between IL-4 and IL-6 in peripheral blood. Conclusion during the multicycle chemotherapy of newly diagnosed lung cancer patients, the levels of CD8 ~ T lymphocytes CD19 ~ B lymphocytes and CD16 ~ CD56 ~ NK cells down-regulate the number of CD4 ~ T lymphocytes and increase the expression of co-suppressor molecules PD-1, CTLA-4 and CCR-4 on the surface of T cells. Monitoring the changes of the above indexes is of great significance for the formulation of combined chemotherapy and immunotherapy and the evaluation of prognosis.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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