NSCLC立体定向放疗和常规分割放疗的免疫效应及相关临床分析

发布时间：2018-05-21 05:56

本文选题：非小细胞肺癌 + 立体定向放疗　；参考：《安徽医科大学》2017年硕士论文

【摘要】：【目的】探索非小细胞肺癌(non-small cell lung cancer,NSCLC)患者外周血中淋巴细胞亚群的表达及其与临床病理特征的关系;前瞻性观察立体定向放疗(stereotactic body radiotherapy,SBRT)和常规分割放疗(conventionally fractionated radiotherapy,CFRT)前后外周血中淋巴细胞亚群表达的动态变化,分析两者的异同,并进一步分析淋巴细胞亚群及其变化与SBRT近期疗效的关系;同时分析鳞癌与腺癌患者在SBRT前后淋巴细胞亚群变化的异同。【方法】第一部分:纳入2014年9月至2016年5月就诊于我院放疗科的70例NSCLC患者(40例首次确诊患者、30例首次疾病进展患者)和14例年龄、性别相匹配的健康对照,使用流式细胞仪检测外周血中CD3+T细胞、CD4+T细胞、CD8+T细胞、CD8+CD28+T细胞、CD8+CD28-T细胞、Treg细胞、CD19+B细胞、NK细胞、NKT细胞、γδT细胞的表达,分析NSCLC与健康人以上指标的表达差异及其与临床病理特征的关系。第二部分:前瞻性纳入2015年2月到2016年12月在我院接受放疗的60例NSCLC患者(40例接受SBRT、20例接受CFRT)。于所有患者放疗前1周内、放疗后1周内及放疗后4周左右采集患者外周血,使用流式细胞仪检测上述指标中T淋巴细胞亚群的表达,观察SBRT和CFRT前后T淋巴细胞亚群的变化,进一步分析鳞癌与腺癌患者SBRT前后以上指标的变化,同时分析它们的表达及其变化与SBRT近期疗效的关系。【结果】第一部分:与健康人相比,NSCLC患者外周血中Treg细胞、CD8+CD28-T细胞、CD8+T细胞比例显著升高,CD4+T细胞、CD4/CD8比值下降(P0.05),尤其在出现首次进展的NSCLC患者中表现更为明显。患者的年龄越小,CD3+T细胞和CD4+T细胞越高(P0.05);女性组CD4+T细胞比例和CD4/CD8比值明显高于男性组(P0.05);不吸烟组γδT细胞比例显著高于吸烟组(P=0.011);肿瘤标志物阴性组CD3+T细胞、CD8+T细胞、CD8+CD28+T细胞比例均高于肿标阳性组(P=0.049、0.026、0.050)。第二部分:1.与SBRT前相比,治疗后NSCLC患者外周血中CD4+T细胞比例和CD4/CD8比值出现明显升高(P=0.032、0.022);4周后CD3+T细胞比例、CD8+T细胞比例、CD8+CD28-T细胞比例出现明显升高(P=0.004、0.015、0.031),而具有免疫抑制功能的Treg细胞无变化。与CFRT前相比,治疗后NSCLC患者外周血中CD8+CD28+T细胞比例出现明显下降(P=0.010),具有免疫抑制功能的Treg细胞比例出现显著升高(P=0.022);4周后CD4+T细胞比例、CD4/CD8比值、CD8+CD28+T细胞比例明显降低(P=0.011、0.004、0.004),CD8+T细胞比例和CD8+CD28-T细胞比例明显升高(P=0.010、0.001)。2.进一步分析鳞癌和腺癌SBRT后的免疫改变发现:与治疗前相比,NSCLC鳞癌患者SBRT后CD8+T细胞有下降趋势(P=0.149),4周后CD8+T细胞比例呈上升趋势(P=0.098)、CD4/CD8比值出现下降趋势(P=0.057);NSCLC腺癌患者SBRT后CD4+T细胞比例和CD4/CD8比值有升高倾向(P=0.110、0.101),4周后CD3+T细胞比例明显上升(P=0.009),CD8+T细胞和CD8+CD28-T细胞比例出现升高趋势(P=0.079、0.064)。3.Treg细胞比例以及SBRT后CD8+T细胞比例的升高、CD4/CD8比值的下降与SBRT的近期疗效存在相关性(P0.05)。【结论】外周血淋巴细胞亚群检测结果提示NSCLC患者机体存在一定程度的免疫抑制,且在出现疾病进展时抑制更为明显;患者的年龄、性别、吸烟史、肿瘤标志物与淋巴细胞亚群的表达存在相关性;SBRT激活NSCLC患者机体免疫应答的作用在一定程度上优于CFRT;SBRT对NSCLC患者免疫状态的影响可能存在时间窗;鳞癌和腺癌接受SBRT治疗后产生的免疫反应有所不同;Treg细胞比例与SBRT疗效呈负相关,SBRT后CD8+T细胞比例的升高、CD4/CD8比值降低与近期疗效呈正相关。
[Abstract]:[Objective] to explore the expression of lymphocyte subsets in peripheral blood of patients with non-small cell lung cancer (NSCLC) and its relationship with the clinicopathological features; the prospective observation of stereotactic radiotherapy (stereotactic body radiotherapy, SBRT) and conventional fractionated radiotherapy (conventionally fractionated radiotherapy) The dynamic changes in the expression of lymphocyte subsets in the peripheral blood were analyzed, and the relationship between the lymphocyte subsets and the changes of the lymphocyte subsets and the short-term effect of SBRT was further analyzed. At the same time, the differences and similarities between the lymphocyte subsets in the squamous cell and adenocarcinoma patients before and after the SBRT were analyzed. [Methods] the first part was included in our hospital from September 2014 to May 2016. 70 NSCLC patients (40 first confirmed patients, 30 first disease progression) and 14 age and sex matched healthy controls were used to detect CD3+T cells, CD4+T cells, CD8+T cells, CD8+CD28+T cells, CD8+CD28-T cells, Treg cells, CD19+B cells, NK cells, NKT cells, and T cells in the peripheral blood. Analysis of the difference in expression of NSCLC and the above indicators and its relationship with the clinicopathological features. Second part: prospectively included 60 patients with NSCLC receiving radiotherapy in our hospital from February 2015 to December 2016 (40 cases received SBRT, 20 patients receiving CFRT). Within 1 weeks before radiotherapy, 1 weeks after radiotherapy and 4 weeks after radiotherapy in all patients. In peripheral blood, the expression of T lymphocyte subsets in the above indexes was detected by flow cytometry, and the changes of T lymphocyte subsets before and after SBRT and CFRT were observed. The changes of the above indexes before and after SBRT in squamous and adenocarcinoma patients were further analyzed, and the relationship between their expression and their changes and the short-term effect of SBRT was analyzed. [results] Part 1: Compared with healthy people, the proportion of Treg cells, CD8+CD28-T cells, and CD8+T cells in the peripheral blood of NSCLC patients increased significantly, and the ratio of CD4+T cells and CD4/CD8 decreased (P0.05), especially in the NSCLC patients who had first progresses. The younger the patients, the higher the CD3+T and CD4+T cells (P0.05), the proportion of CD4+T cells in female groups and those of the women. The ratio was significantly higher than that in the male group (P0.05); the ratio of gamma delta T cells in the non smoking group was significantly higher than that in the smoking group (P=0.011); the proportion of CD3+T cells, CD8+T cells and CD8+CD28+T cells in the negative group of tumor markers was higher than that of the swollen mark positive group (P=0.049,0.026,0.050). The second part: compared with the before SBRT, the ratio and CD4/ of CD4+T cells in the peripheral blood of the patients after the treatment were compared with those before the treatment. The ratio of CD8 increased significantly (P=0.032,0.022). After 4 weeks, the proportion of CD3+T cells, the proportion of CD8+T cells, the proportion of CD8+CD28-T cells increased significantly (P=0.004,0.015,0.031), but the Treg cells with immunosuppressive function were not changed. Compared with before CFRT, the percentage of CD8+CD28+T cells in the peripheral blood of patients with NSCLC decreased significantly (P=0.010). The proportion of Treg cells with immunosuppressive function increased significantly (P=0.022); the proportion of CD4+T cells, the ratio of CD4/CD8, the proportion of CD8+CD28+T cells decreased significantly after 4 weeks (P=0.011,0.004,0.004), the proportion of CD8+T cells and the proportion of CD8+CD28-T cells increased significantly (P=0.010,0.001).2. further analysis of immune changes after squamous cell carcinoma and adenocarcinoma SBRT: Compared with before treatment, CD8+T cells in NSCLC squamous cell carcinoma decreased after SBRT (P=0.149). After 4 weeks, the proportion of CD8+T cells increased (P=0.098), and the CD4/CD8 ratio decreased (P=0.057). The proportion of CD4+T cells and CD4/CD8 ratios in NSCLC adenocarcinoma patients were higher after SBRT, and the proportion of cells increased significantly after 4 weeks. 09) the proportion of CD8+T cells and CD8+CD28-T cells increased (P=0.079,0.064).3.Treg cell ratio and the increase of CD8+T cell ratio after SBRT, and the decrease of CD4/CD8 ratio was associated with the short-term effect of SBRT (P0.05). [Conclusion] the test results of peripheral blood lymphocyte subsets suggest that there is a certain degree of immunity in the body of NSCLC patients. The effect of SBRT on the immune response of patients with NSCLC is better than that of CFRT; the effect of SBRT on the immune status of NSCLC patients may have a time window; squamous cell carcinoma and the effect of SBRT on the immune status of NSCLC patients; The immune responses of adenocarcinoma treated with SBRT were different. The proportion of Treg cells was negatively correlated with the effect of SBRT, the proportion of CD8+T cells increased after SBRT, and the decrease of CD4/CD8 ratio was positively correlated with the short-term effect.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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