本文選題：卵巢癌 + 免疫治療��； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的探討Ep CAM蛋白激活樹突細(xì)胞(DC)誘導(dǎo)產(chǎn)生CD8+細(xì)胞毒T淋巴細(xì)胞(CD8+CTL)進(jìn)行卵巢癌免疫治療的效果,為卵巢癌的臨床治療提供幫助。方法利用Ep CAM蛋白誘導(dǎo)成熟DC同時(shí)檢測(cè)DC表面分子和白介素(IL-10與IL-12)表達(dá)量的變化,隨后通過(guò)Ep CAM-DC誘導(dǎo)Ep CAM抗原特異性CD8+CTL,繼而檢測(cè)Ep CAM-DC-CD8+CTL對(duì)正常卵巢上皮細(xì)胞IOSE80和卵巢癌細(xì)胞SKOV3的殺傷效果,同時(shí)檢測(cè)干擾素(IFN)-γ釋放量。隨后進(jìn)一步檢測(cè)Ep CAM-DC-CD8+CTL對(duì)卵巢癌移植裸鼠的腫瘤抑制效果,并通過(guò)病理學(xué)染色比較治療前后腫瘤組織變化情況。結(jié)果與PBS刺激相比,Ep CAM蛋白能夠顯著上調(diào)DC表面分子CD80、CD83、CD86和HLA-DR水平,依次達(dá)到4.79、4.85、4.60和10.91倍;同時(shí)Ep CAM蛋白顯著提高IL-12釋放和顯著抑制IL-10分泌(P0.05)。DC-CD8+CTL與Ep CAM-DC-CD8+CTL均引起少量IOSE80細(xì)胞凋亡(P0.05),但Ep CAM-DC-CD8+CTL對(duì)SKOV3細(xì)胞殺傷率是DC-CD8+CTL的6.82倍(P0.05)。動(dòng)物實(shí)驗(yàn)表明,經(jīng)Ep CAM-DC-CD8+CTL治療后,BALB/C-nu/nu卵巢癌移植腫瘤體積比明顯低于PBS組以及DC-CD8+CTL組,分別達(dá)到0.27和0.28倍(P0.05)。HE染色顯示Ep CAM-DC-CD8+CTL治療導(dǎo)致腫瘤組織出現(xiàn)明顯的病理學(xué)改變。結(jié)論Ep CAM蛋白刺激促進(jìn)了DC成熟繼而誘導(dǎo)產(chǎn)生Ep CAM特異性CD8+CTL,Ep CAM-DC-CD8+CTL能夠高效的殺傷腫瘤細(xì)胞并延遲腫瘤生長(zhǎng),對(duì)卵巢癌臨床免疫治療具有重要意義。
[Abstract]:Objective to investigate the effect of immunotherapy of ovarian cancer with Ep CAM protein activated dendritic cell (DC) induced CD8 cytotoxic T lymphocytes (CD8 CTL), and to provide help for clinical treatment of ovarian cancer. Methods mature DCs were induced by EP CAM protein to detect the expression of IL-10 and IL-12 on the surface of DCs at the same time. Then Ep CAM antigen-specific CD8 CTLs were induced by EP CAM-DC, then the killing effect of EP CAM-DC-CD8 CTL on normal ovarian epithelial cells IOSE80 and ovarian cancer cells SKOV3 was detected, and the release of IFN- 緯 from IFN- 緯 was detected. Then the tumor inhibition effect of EP CAM-DC-CD8 CTL on nude mice transplanted with ovarian cancer was further detected, and the changes of tumor tissue before and after treatment were compared by pathological staining. Results compared with PBS stimulation, Ep CAM protein could significantly upregulate the levels of CD80, CD83, CD86 and HLA-DR on DC surface, which were 4.79 ~ 4.85 ~ 4.60 and 10.91 times respectively. At the same time, EP CAM protein significantly increased the release of IL-12 and significantly inhibited the secretion of IL-10 by P0.05N. DC-CD8 CTL and EP CAM-DC-CD8 CTL both induced a small amount of IOSE80 cell apoptosis, but the killing rate of EP CAM-DC-CD8 CTL on SKOV3 cells was 6.82 times as high as that of DC-CD8 CTL. Animal experiments showed that the tumor volume ratio of BALB / C-nunu ovarian cancer transplanted after Ep CAM-DC-CD8 CTL therapy was significantly lower than that of PBS group and DC-CD8 CTL group, and reached 0.27 and 0.28 times P0.05U. He staining showed that EP CAM-DC-CD8 CTL treatment resulted in obvious pathological changes in tumor tissue. Conclusion Ep CAM protein stimulates DC maturation and then induces the production of EP CAM specific CD8 CAM-DC-CD8 CTL, which can effectively kill tumor cells and delay tumor growth. It is of great significance for clinical immunotherapy of ovarian cancer.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.31

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