本文選題：免疫治療 + 淋巴細(xì)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�；熍c免疫治療的結(jié)合,可以增強(qiáng)腫瘤抗原性、活化免疫功能,從而有效啟動(dòng)機(jī)體抗腫瘤免疫。然而,由于化療藥物對(duì)機(jī)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(gè)體的免疫功能狀態(tài)的差異性等等因素,將導(dǎo)致治療過(guò)程中機(jī)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(shí)機(jī)仍需探索。目的研究初診肺癌患者多次化療過(guò)程中,外周血淋巴細(xì)胞亞群數(shù)量、T淋巴細(xì)胞表面共信號(hào)分子、細(xì)胞因子等指標(biāo)動(dòng)態(tài)變化趨勢(shì),藉此觀察治療過(guò)程中機(jī)體免疫狀態(tài)的變化趨勢(shì),評(píng)價(jià)患者全身免疫功能狀況,多角度窺探化療過(guò)程中機(jī)體錯(cuò)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(diǎn),為臨床免疫治療介入提供實(shí)驗(yàn)依據(jù)。方法采用流式細(xì)胞術(shù)檢測(cè)23例初診肺癌患者5周期治療前外周血中T淋巴細(xì)胞及其亞群數(shù)量、B淋巴細(xì)胞數(shù)量、NK細(xì)胞數(shù)量,T細(xì)胞表面共信號(hào)分子表達(dá)及細(xì)胞因子表達(dá);收集患者臨床資料及常規(guī)實(shí)驗(yàn)室檢查數(shù)據(jù)。分析從第一周期到第五周期治療過(guò)程中,上述指標(biāo)變化趨勢(shì)是否具有差異。應(yīng)用Flowjo 7.6.1進(jìn)行流式圖分析,應(yīng)用SPSS 20.0軟件進(jìn)行統(tǒng)計(jì)分析。所有計(jì)量數(shù)據(jù)均用（？）±s表示,兩組間的比較采用獨(dú)立樣本t檢驗(yàn),P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果1. 通過(guò)收集23例肺癌患者的資料,統(tǒng)計(jì)分析發(fā)現(xiàn),多次化療過(guò)程中外周血白細(xì)胞、中性粒細(xì)胞、淋巴細(xì)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(biāo)變化不顯著;3.CD8~+T淋巴細(xì)胞、CD19~+B淋巴細(xì)胞和CD16~+CD56~+NK細(xì)胞水平下調(diào),CD4~+T淋巴細(xì)胞數(shù)量增加;4.CD8~+T淋巴細(xì)胞表面PD-1、CTLA-4和CCR-4表達(dá)上調(diào),PD-L1表達(dá)水平下調(diào),CD137整體表達(dá)無(wú)明顯差異;5.CD4~+T淋巴細(xì)胞表面PD-1表達(dá)上調(diào),PD-L1表達(dá)下調(diào),CTLA-4、LAG-3、CCR-4和CD137表達(dá)整體變化不顯著;6.外周血中細(xì)胞因子(IL-2、IFN-γ、IL-4、IL-6、IL-10、TNF-α和IL-17A)整體表達(dá)無(wú)顯著差異。結(jié)論初診肺癌患者多周期化療過(guò)程中,機(jī)體CD8~+T淋巴細(xì)胞、CD19~+B淋巴細(xì)胞和CD16~+CD56~+NK細(xì)胞水平下調(diào),CD4~+T淋巴細(xì)胞數(shù)量增加;T細(xì)胞表面共抑制分子PD-1、CTLA-4和CCR-4隨治療進(jìn)行表達(dá)下調(diào),監(jiān)測(cè)上述指標(biāo)變化對(duì)化療聯(lián)合免疫治療綜合治療方案制定、預(yù)后評(píng)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(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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