本文選題：免疫治療 + 淋巴細胞亞群��； 參考：《新鄉(xiāng)醫(yī)學(xué)院》2017年碩士論文

【摘要】：背景肺癌已成為全世界范圍內(nèi)發(fā)病率和死亡率居首位的惡性腫瘤。隨著分子免疫學(xué)的研究發(fā)展,免疫治療日趨成為繼手術(shù)、化療、放療之后的一種重要治療手段。化療與免疫治療的結(jié)合,可以增強腫瘤抗原性、活化免疫功能,從而有效啟動機體抗腫瘤免疫。然而,由于化療藥物對機體免疫功能的影響與藥物種類、劑量、給藥方式等密切相關(guān),加之不同個體的免疫功能狀態(tài)的差異性等等因素,將導(dǎo)致治療過程中機體免疫功能狀態(tài)復(fù)雜多變,化療與免疫治療的有利組合時機仍需探索。目的研究初診肺癌患者多次化療過程中,外周血淋巴細胞亞群數(shù)量、T淋巴細胞表面共信號分子、細胞因子等指標動態(tài)變化趨勢,藉此觀察治療過程中機體免疫狀態(tài)的變化趨勢,評價患者全身免疫功能狀況,多角度窺探化療過程中機體錯綜復(fù)雜的免疫功能變化,探索免疫治療與化療結(jié)合的有利切入點,為臨床免疫治療介入提供實驗依據(jù)。方法采用流式細胞術(shù)檢測23例初診肺癌患者5周期治療前外周血中T淋巴細胞及其亞群數(shù)量、B淋巴細胞數(shù)量、NK細胞數(shù)量,T細胞表面共信號分子表達及細胞因子表達;收集患者臨床資料及常規(guī)實驗室檢查數(shù)據(jù)。分析從第一周期到第五周期治療過程中,上述指標變化趨勢是否具有差異。應(yīng)用Flowjo 7.6.1進行流式圖分析,應(yīng)用SPSS 20.0軟件進行統(tǒng)計分析。所有計量數(shù)據(jù)均用（？）±s表示,兩組間的比較采用獨立樣本t檢驗,P0.05為差異有統(tǒng)計學(xué)意義。結(jié)果1. 通過收集23例肺癌患者的資料,統(tǒng)計分析發(fā)現(xiàn),多次化療過程中外周血白細胞、中性粒細胞、淋巴細胞、血小板、血紅蛋白的水平顯著下降;2.患者血生化(總蛋白、白蛋白、球蛋白、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶、葡萄糖)指標變化不顯著;3.CD8~+T淋巴細胞、CD19~+B淋巴細胞和CD16~+CD56~+NK細胞水平下調(diào),CD4~+T淋巴細胞數(shù)量增加;4.CD8~+T淋巴細胞表面PD-1、CTLA-4和CCR-4表達上調(diào),PD-L1表達水平下調(diào),CD137整體表達無明顯差異;5.CD4~+T淋巴細胞表面PD-1表達上調(diào),PD-L1表達下調(diào),CTLA-4、LAG-3、CCR-4和CD137表達整體變化不顯著;6.外周血中細胞因子(IL-2、IFN-γ、IL-4、IL-6、IL-10、TNF-α和IL-17A)整體表達無顯著差異。結(jié)論初診肺癌患者多周期化療過程中,機體CD8~+T淋巴細胞、CD19~+B淋巴細胞和CD16~+CD56~+NK細胞水平下調(diào),CD4~+T淋巴細胞數(shù)量增加;T細胞表面共抑制分子PD-1、CTLA-4和CCR-4隨治療進行表達下調(diào),監(jiān)測上述指標變化對化療聯(lián)合免疫治療綜合治療方案制定、預(yù)后評估具有重要意義。
[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 鹵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- 偽 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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R734.2

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