本文關(guān)鍵詞： 髓源抑制細(xì)胞 免疫抑制 免疫逃逸 EP方案 TP方案 小細(xì)胞肺癌　出處：《吉林大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景: 肺癌是當(dāng)前世界范圍內(nèi)最常見的惡性腫瘤，手術(shù)治療聯(lián)合放化療還是目前治療肺癌的方式，但事實上，絕大多數(shù)肺癌患者在就診時或臨床確診時就已經(jīng)失去了手術(shù)治療的機會，而其中一部分患者，即便進(jìn)行了手術(shù)治療，仍然存在較高的轉(zhuǎn)移和復(fù)發(fā)率。因此，在肺癌的治療手段上需要一種更有效的方法。近年來，腫瘤的生物免疫治療方法出現(xiàn)在臨床應(yīng)用當(dāng)中，它可以提高腫瘤患者的抗腫瘤免疫功能。免疫和腫瘤之間關(guān)系密切、藕斷絲連，免疫在一方面在腫瘤的形成過程中起到了一定作用，如預(yù)防腫瘤的形成并形成免疫監(jiān)視等；但是在慢性炎癥等慢性過程的時候，由于其重要的免疫學(xué)特性，髓系抑制細(xì)胞參與重要的稱為腫瘤的免疫抑制和免疫逃逸機制的過程，是影響生物免疫治療的一個重要因素。隨著對腫瘤微環(huán)境鉆研的深入，髓源抑制細(xì)胞（MDSCs）在腫瘤患者外周血和組織中的比例顯著高于正常人，是參與免疫抑制和免疫逃逸從而影響腫瘤治療效果的主要因素之一。 目的: 目前已有許多關(guān)于MDSCs的研究，，根據(jù)表面標(biāo)記物可以把它分為單核系和粒系，并發(fā)現(xiàn)了不同類型腫瘤的髓源抑制細(xì)胞的表型和分布數(shù)量存在差異。已有的研究發(fā)現(xiàn)髓源抑制細(xì)胞在各類型的惡性腫瘤中都有異常聚集，并與患者的預(yù)后息息相關(guān)。本研究則標(biāo)記MDSCs上的CD14+/CD33+/CD11b+抗體，運用流式細(xì)胞儀對III、IV期小細(xì)胞肺癌患者化療前后外周血中單核及粒細(xì)胞的百分比檢測，分析不同的化療方案對不同分期的小細(xì)胞肺癌患者髓源抑制細(xì)胞分化的影響，研究化療方案與預(yù)后是否相關(guān)，并進(jìn)一步探討其臨床意義。 方法: 1.選取吉林省長春市吉林大學(xué)中日聯(lián)誼醫(yī)院呼吸內(nèi)科2013年10月-2014年11月期間就診并采用不同化療方案的小細(xì)胞肺癌III期、IV期患者80例，病理學(xué)均已明確小細(xì)胞癌的診斷（詳見論文后附圖1、2）。平均分成八組，每組10人，選取正常健康人群10例。將這些人群統(tǒng)一編號成A、B、C、D、E、F、G、H、I，這些組中A、B、C、G患者為III期、D、E、F、H為IV期，I組為健康人群，A、D兩組為EP方案；B、E兩組為TP方案；C、F兩組均有化療禁忌癥；G、H兩組為TP+EP。 2.通過對這些人群中外周血的采取、對以上人群的CD11b+、CD14+、CD33+進(jìn)行標(biāo)記，通過流式細(xì)胞儀進(jìn)行檢測，可對腫瘤患者用藥前后的髓源抑制細(xì)胞的含量進(jìn)行分析，對健康人群中髓源抑制細(xì)胞的含量進(jìn)行分析。最終對采集來的數(shù)據(jù)進(jìn)行有效的歸納總結(jié)和處理。對分組采集后的結(jié)果通過卡方檢驗、t檢驗以及平均數(shù)±標(biāo)準(zhǔn)差的辦法進(jìn)行統(tǒng)計學(xué)的量化。并對統(tǒng)計的結(jié)果進(jìn)行比對確定髓源抑制細(xì)胞和小細(xì)胞肺癌之間的關(guān)系、髓源抑制細(xì)胞和EP化療方案之間的關(guān)系、髓源抑制細(xì)胞和TP化療方案之間的關(guān)系、不同分期的小細(xì)胞肺癌與TP化療方案之間的關(guān)系、不同分期的小細(xì)胞肺癌與EP化療方案之間的關(guān)系、TP化療方案與EP化療方案之間的關(guān)系、髓源抑制細(xì)胞與正常人之間的關(guān)系。 結(jié)果: 1.EP方案在小細(xì)胞肺癌III期患者的效果較明顯 2.TP方案在小細(xì)胞肺癌IV期患者的作用效果較明顯 3.兩種方案聯(lián)合后數(shù)值并沒有出現(xiàn)明顯的變化 4.通過腫瘤人群與正常人群的對比，髓源抑制細(xì)胞的含量可與腫瘤的發(fā)生發(fā)展過程有著密切的聯(lián)系（P0.05） 5.通過用藥后與用藥前的人群對比，化療藥物是通過抑制髓源抑制細(xì)胞的生成來達(dá)到對小細(xì)胞肺癌的控制作用（P0.05） 6. TP方案與EP方案的選擇上，無論選擇哪種方案，都對髓源抑制細(xì)胞增殖的抑制有著重要的作用（P0.05） 結(jié)論: 1.在小細(xì)胞肺癌III期、IV期患者當(dāng)中運用EP化療方案會有更顯著的療效 2.兩種方案聯(lián)合與單一用藥療效差異不顯著 3.髓源抑制細(xì)胞在腫瘤患者的機體內(nèi)具有更大的出現(xiàn)比例 4.腫瘤患者在使用化療方案后髓源抑制細(xì)胞的數(shù)量可以下降到接近于正常人群的水平
[Abstract]:Research background:
Lung cancer is currently the world's most common malignant tumor, surgical treatment combined with radiotherapy and chemotherapy is the treatment of lung cancer, but in fact, the vast majority of lung cancer patients in the clinic or clinical diagnosis have lost the opportunity of surgical treatment, and some patients, even if the surgical treatment, recurrence and metastasis still exist the higher the rate. Therefore, the need for a more effective method in the treatment of lung cancer means. In recent years, the biological immune therapy of cancer in clinical application, it can improve the anti-tumor immune function of tumor patients. The relationship between immune and tumor immune ouduansilian closely, on the one hand, in the formation of tumor in the play a role, such as the prevention of tumor formation and the formation of immune surveillance; but when the chronic inflammation and chronic process, because of its important immunological characteristics, Myeloid suppressor cells participate in the important process known as immune suppression and tumor immune escape mechanisms, is an important factor affecting the immune therapy of the tumor microenvironment. With the in-depth study, myeloid derived suppressor cells (MDSCs) in the peripheral blood and tissues than patients was higher than that of normal. Is one of the main factors involved in immune suppression and immune escape and thus influence the tumor therapeutic effect.
Objective:
There are many studies about MDSCs, according to the surface markers can be divided into granulocyte and monocyte lineages, and found different tumor types of myeloid derived suppressor cells phenotype and the distribution of the number of differences. It has been found that myeloid derived suppressor cells are in various types of malignant tumors and abnormal aggregation. Closely related to the prognosis of the patients. This study is labeled CD14+/CD33+/CD11b+ antibody on MDSCs, the use of III flow cytometry, the percentage of IV phase detection before and after chemotherapy in patients with non-small cell lung cancer in peripheral blood monocytes and granulocytes, analysis of the effect of different chemotherapy regimens for different patients with small cell lung cancer staging of myeloid cell differentiation inhibition the study on whether chemotherapy and prognosis, and further explore its clinical significance.
Method:
1. city of Jilin province were Changchun Japan Union Hospital of Jilin University Department of respiratory medicine in October 2013 -2014 year in November during the visit and the chemotherapy in small cell lung cancer of stage III, 80 cases of IV patients, the pathological diagnosis of small cell carcinoma have been clear (see the figure 1,2). The average divided into eight groups, each group of 10 people select normal, 10 cases of healthy people. These people number into A, B, C, D, E, F, G, H, I, B, A groups, C, G in patients with stage III, D, E, F, H, IV, I group of healthy people. A D, the two group was EP B, two E; group C, F TP; the two groups had contraindications to chemotherapy; G, H two group was TP+EP.
2. by taking on these populations of peripheral blood, the people of more than CD11b+, CD14+, CD33+ markers were detected by flow cytometry, analyzing the content of tumor patients before and after treatment of myeloid derived suppressor cells, the content of bone marrow derived in healthy population cells were analyzed. The final acquisition of the data were summarized and effective treatment. After the collection of packet results through chi square test, t test and quantitative statistical average standard deviation method. And the statistical results were compared to determine the relationship between myeloid derived suppressor cells and small cell lung cancer, myeloid derived suppressor cells and the relationship between EP chemotherapy, myeloid derived suppressor cells and the relationship between TP chemotherapy, the relationship between the different stages of the small cell lung cancer with TP chemotherapy, different stages of small cell lung cancer with EP regimen between Relationship, the relationship between the TP chemotherapy regimen and the EP chemotherapy regimen, the relationship between the myelinated suppressor cells and the normal person.
Result:
The effect of 1.EP scheme in patients with stage III of small cell lung cancer is more obvious
The effect of 2.TP scheme in patients with stage IV of small cell lung cancer is more obvious
3. there are no obvious changes in the combined value of the two schemes.
4. through the contrast between the tumor population and the normal population, the content of the myelinated suppressor cells can be closely related to the development of the tumor (P0.05).
5. the chemotherapeutic drugs are controlled by inhibiting the formation of myelinated suppressor cells to control small cell lung cancer (P0.05).
The selection of the 6. TP scheme and the EP scheme, regardless of which option, has an important effect on the inhibition of the proliferation of myelinated myeloid cells (P0.05)
Conclusion:
1. in phase III of small cell lung cancer, the use of EP chemotherapy in IV patients will have a more significant effect.
2. the difference between the combination of the two schemes and the single medication was not significant
3. medullary suppressor cells have a greater proportion in the body of the cancer patients
4. the number of medullary suppressor cells in the cancer patients can fall to the level of the normal population after using the chemotherapy regimen.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R734.2

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