本文選題：非小細胞肺癌 + 立體定向放療�。� 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：【目的】探索非小細胞肺癌(non-small cell lung cancer,NSCLC)患者外周血中淋巴細胞亞群的表達及其與臨床病理特征的關(guān)系;前瞻性觀察立體定向放療(stereotactic body radiotherapy,SBRT)和常規(guī)分割放療(conventionally fractionated radiotherapy,CFRT)前后外周血中淋巴細胞亞群表達的動態(tài)變化,分析兩者的異同,并進一步分析淋巴細胞亞群及其變化與SBRT近期療效的關(guān)系;同時分析鱗癌與腺癌患者在SBRT前后淋巴細胞亞群變化的異同�！痉椒ā康谝徊糠�:納入2014年9月至2016年5月就診于我院放療科的70例NSCLC患者(40例首次確診患者、30例首次疾病進展患者)和14例年齡、性別相匹配的健康對照,使用流式細胞儀檢測外周血中CD3+T細胞、CD4+T細胞、CD8+T細胞、CD8+CD28+T細胞、CD8+CD28-T細胞、Treg細胞、CD19+B細胞、NK細胞、NKT細胞、γδT細胞的表達,分析NSCLC與健康人以上指標的表達差異及其與臨床病理特征的關(guān)系。第二部分:前瞻性納入2015年2月到2016年12月在我院接受放療的60例NSCLC患者(40例接受SBRT、20例接受CFRT)。于所有患者放療前1周內(nèi)、放療后1周內(nèi)及放療后4周左右采集患者外周血,使用流式細胞儀檢測上述指標中T淋巴細胞亞群的表達,觀察SBRT和CFRT前后T淋巴細胞亞群的變化,進一步分析鱗癌與腺癌患者SBRT前后以上指標的變化,同時分析它們的表達及其變化與SBRT近期療效的關(guān)系�！窘Y(jié)果】第一部分:與健康人相比,NSCLC患者外周血中Treg細胞、CD8+CD28-T細胞、CD8+T細胞比例顯著升高,CD4+T細胞、CD4/CD8比值下降(P0.05),尤其在出現(xiàn)首次進展的NSCLC患者中表現(xiàn)更為明顯�；颊叩哪挲g越小,CD3+T細胞和CD4+T細胞越高(P0.05);女性組CD4+T細胞比例和CD4/CD8比值明顯高于男性組(P0.05);不吸煙組γδT細胞比例顯著高于吸煙組(P=0.011);腫瘤標志物陰性組CD3+T細胞、CD8+T細胞、CD8+CD28+T細胞比例均高于腫標陽性組(P=0.049、0.026、0.050)。第二部分:1.與SBRT前相比,治療后NSCLC患者外周血中CD4+T細胞比例和CD4/CD8比值出現(xiàn)明顯升高(P=0.032、0.022);4周后CD3+T細胞比例、CD8+T細胞比例、CD8+CD28-T細胞比例出現(xiàn)明顯升高(P=0.004、0.015、0.031),而具有免疫抑制功能的Treg細胞無變化。與CFRT前相比,治療后NSCLC患者外周血中CD8+CD28+T細胞比例出現(xiàn)明顯下降(P=0.010),具有免疫抑制功能的Treg細胞比例出現(xiàn)顯著升高(P=0.022);4周后CD4+T細胞比例、CD4/CD8比值、CD8+CD28+T細胞比例明顯降低(P=0.011、0.004、0.004),CD8+T細胞比例和CD8+CD28-T細胞比例明顯升高(P=0.010、0.001)。2.進一步分析鱗癌和腺癌SBRT后的免疫改變發(fā)現(xiàn):與治療前相比,NSCLC鱗癌患者SBRT后CD8+T細胞有下降趨勢(P=0.149),4周后CD8+T細胞比例呈上升趨勢(P=0.098)、CD4/CD8比值出現(xiàn)下降趨勢(P=0.057);NSCLC腺癌患者SBRT后CD4+T細胞比例和CD4/CD8比值有升高傾向(P=0.110、0.101),4周后CD3+T細胞比例明顯上升(P=0.009),CD8+T細胞和CD8+CD28-T細胞比例出現(xiàn)升高趨勢(P=0.079、0.064)。3.Treg細胞比例以及SBRT后CD8+T細胞比例的升高、CD4/CD8比值的下降與SBRT的近期療效存在相關(guān)性(P0.05)�！窘Y(jié)論】外周血淋巴細胞亞群檢測結(jié)果提示NSCLC患者機體存在一定程度的免疫抑制,且在出現(xiàn)疾病進展時抑制更為明顯;患者的年齡、性別、吸煙史、腫瘤標志物與淋巴細胞亞群的表達存在相關(guān)性;SBRT激活NSCLC患者機體免疫應(yīng)答的作用在一定程度上優(yōu)于CFRT;SBRT對NSCLC患者免疫狀態(tài)的影響可能存在時間窗;鱗癌和腺癌接受SBRT治療后產(chǎn)生的免疫反應(yīng)有所不同;Treg細胞比例與SBRT療效呈負相關(guān),SBRT后CD8+T細胞比例的升高、CD4/CD8比值降低與近期療效呈正相關(guān)。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2

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