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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山 | |
| dc.contributor.author | Pei-Ju Hsu | en |
| dc.contributor.author | 徐珮茹 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:20:26Z | - |
| dc.date.available | 2013-08-08 | |
| dc.date.copyright | 2008-08-08 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-23 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37165 | - |
| dc.description.abstract | 在口腔中超過95%的惡性腫瘤為口腔鱗狀上皮細胞癌，並且為台灣六大常見侵襲癌症死因之ㄧ，然而，口腔癌的高發生率與咀嚼檳榔的習性有關。人類產生在不同器官或組織的癌症，其疾病起因除了基因毒性和致癌基因突變外，目前免疫編輯(immune-editing)也被視為一個重要的因素。為研究在人類口腔鱗狀細胞腫瘤微環境之內調節性T細胞(Tregs)的分布，利用流式細胞儀直接分析在體內的腫瘤浸潤淋巴細胞(TIL)表現各種調節性T細胞的標記分子。結果顯示，在口腔鱗狀細胞癌病患之腫瘤組織內浸潤CD3+CD4+之淋巴細胞中，CD25+T細胞所佔比例為22.8±8.7%，相對於病患之週邊血液中的比例為7.8 ±5.6 %，此增加具有統計上的意義(p＜0.0001)。此外，Foxp3在CD4+CD25+調節性T細胞作用及發展中，是重要的轉錄因子，並且和CD25表現量具有相關性。藉由CD25表現之螢光強度，將腫瘤浸潤及周邊血液中CD4+T淋巴球分為:高度表現CD25和Foxp3細胞亞群(CD25highFoxp3high)、中度表現CD25和Foxp3細胞亞群(CD25intermediateFoxp3intermediate)、低度表現CD25和Foxp3細胞亞群(CD25lowFoxp3low)。CD25low和CD25intermediate細胞亞群分別表現大量、或低量的IL-2及IL-10；然而CD25high細胞亞群幾乎不會表現這兩種細胞激素。另外，也發現有CD4+CD25-Foxp3-之T細胞會分泌IL-10，可能為第ㄧ型調節性T細胞(Tr1)。CD4+CD25+Foxp3high之調節性T細胞，具有抑制自體的CD4+CD25-T細胞增生的能力。在腫瘤基質細胞T細胞混合培養系統中，腫瘤基質細胞可以使增加CD3+T細胞分泌IFN-γ、IL-2、TNF-α，卻不能表現IL-4。因此，本研究發現有不同特性的調節性T細胞亞群，浸潤於口腔鱗狀上皮細胞癌中。 | zh_TW |
| dc.description.abstract | Oral squamous cell carcinoma (OSCC) accounts for more than 95% of all malignant neoplasms in the oral cavity, and ranks as the sixth major cause of cancer mortality in Taiwan. The high incidence of oral cancer is associated with the habit of chewing areca nut preparations. In addition to genotoxic effects and oncogenic mutations etc, immune-editing is currently regarded as one of the important etiological elements in human cancers. To investigate the distribution of regulatory T lymphocytes (Tregs) within tumor microenvironment in human oral squamous cell carcinoma (OSCC), the in vivo expressions of various Treg markers on tumor-infiltrating lymphocyte (TIL) was directly examined by flow cytometry. The results indicate that, in TIL, proportion of distinct CD25+ cells in the CD3+CD4+ subset (22.8±8.7%) were enriched relative to that found in PBMC (7.8 ±5.6 %) from OSCC patients (p＜0.0001). FoxP3, a key transcription factor for CD4+CD25+ Tregs development and function, is correlated with the expression of CD25. Based on the expression intensity of CD25, different subsets of CD4+T cell were identified both in TIL and PBMC; CD25highFoxp3high, CD25intermediateFoxp3intermediate, and CD25lowFoxp3low. The CD25low or CD25intermediate subsets produced high or low amounts of IL-2 and IL-10, respectively, whereas CD25high subset scarcely produced these two cytokines. Another IL-10 secreting CD4+CD25-Foxp3-T cells, possibly Tr1 cells, could also be identified. CD4+CD25+Foxp3high Treg exhibits suppressive activity on the proliferation of autologous CD4+CD25- T cells. In coculture system, tumor stroma cells could enhance the production of IFN-γ、IL-2、TNF-α, but not IL-4 in CD3+ T cells. Therefore, there are different subsets of regulatory T cells infiltrated in OSCC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:20:26Z (GMT). No. of bitstreams: 1 ntu-97-R95450007-1.pdf: 2000853 bytes, checksum: 6a6aae76a8d8ba3d4da77a89ffaa6ef5 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………1
英文摘要………………………………………………………………………2 目錄……………………………………………………………………………3 第一章、 緒論…………………………………………………………………6 第一節、相關背景與研究…………………………………………………...6 ㄧ、口腔鱗狀上皮細胞癌………………………………………………….6 二、口腔癌免疫抑制作用………………………………………………….7 三、調節性T細胞(regulatory T cells) …………………………………….9 四、第一型T細胞(Tc1/Th1)與第二型T細胞(Tc2/Th2) …………………12 五、自然殺手細胞受體(natural killer receptor) ………………………….13 第二節、研究動機與目的………………………………………………….15第二章、 實驗分法與材料…………………………………………………..16 第一節、檢體的收集及來源……………………………………………….16 第二節、人類口腔鱗狀上皮細胞癌組織內淋巴球的分離與純化……….16 第三節、人類周邊血液單核球的分離與純化…………………………….17 第四節、細胞表面染色…………………………………………………….17 第五節、細胞內染色……………………………………………………….18 第六節、反應T細胞增生及抑制型T細胞篩選分離方法及細胞增生試驗…………………………………………………………………19 第七節、T細胞與腫瘤基質細胞體外共同培養方法……………………..20 第八節、細胞激素測定…………………………………………………….20 第九節、T淋巴球表面抗原、表面受體及各種細胞分型的百分比表示方法…………………………………………………………………21 第十節、統計分析…………………………………………………………21 第三章、 結果………………………………………………………………..22 第一節、由口腔鱗狀上皮細胞癌病患分離出的腫瘤浸潤淋巴球中CD3+CD8+T淋巴球表現CD94與NKG2A之比例…………..22 第二節、口腔鱗狀上皮細胞癌病患分離出之腫瘤內浸潤淋巴球，表現高比例的CD4+CD25+之調節性T細胞的比例、及其細胞內Foxp3的表現………………………………………………………….22 第三節、不同亞型的調節性T細胞存在於口腔鱗狀上皮細胞腫瘤組織中……………………………………………………………….24 第四節、癌細胞或不同基質細胞在體外細胞培養系統中，對CD4+CD25+之調節性T細胞的分化扮演一個重要角色…………………27 第五節、以體外培養系統分析口腔鱗狀上皮細胞癌刺激T細胞分泌細胞激素………………………………………………………………28 第四章、 討論………………………………………………………………31 第五章、 參考文獻…………………………………………………………38 第六章、 圖表………………………………………………………………..49 圖一、浸潤口腔鱗狀上皮細胞癌組織中和周邊血液的淋巴細胞之表現自 然殺手細胞受體分析……………………………………………….49 圖二、浸潤口腔鱗狀上皮細胞癌組織和周邊血液的淋巴細CD4+CD25+ T細胞分析…………………………………………………………….50 圖三、浸潤口腔鱗狀上皮細胞癌組織和周邊血液的淋巴細胞之表現調節性T細胞標記因子Foxp3分析..........................................................51 圖四、浸潤口腔鱗狀上皮細胞癌組織和周邊血液的淋巴細胞之CD4+CD25low細胞、CD4CD25intermediate細胞、CD4CD25high細胞亞群分析………………………………………………………………52 圖五、口腔鱗狀細胞癌周邊血液中CD4+CD25hi細胞亞群抑制作用…53 圖六、在TIL內不同的CD4+CD25+Foxp3+調節性T細胞亞群分布情形…………………………………………………………………….54 圖七、口腔鱗狀上皮細胞癌的浸潤淋巴細胞之IL-2及IL-10在分裂原刺激之下的表現情形………………………………………………….55 圖八、T細胞和癌細胞、基質細胞體外混合培養中CD4+CD25+T細胞比例之分析…………………………………………………………….56 圖九、T細胞和癌細胞、基質細胞體外混合培養中CD4+CD25+Foxp+ T細胞比例之分析…………………………………………………….57 圖十、體外混合培養的上清液中細胞分泌IFN-γ分析………………58 圖十一、體外混合培養的上清液中細胞分泌IL-2分析………………59 圖十二、體外混合培養的上清液中細胞分泌TNF-α分析……………60 圖十三、體外混合培養的上清液中細胞分泌IL-10分析……………61 表一、所有口腔鱗狀上皮細胞癌病患的臨床病理相關數據…………62 表二、評估比較浸潤口腔鱗狀上皮細胞癌組織中和周邊血液的淋巴細胞之各種T細胞亞群分析……………………………………………..63 表三、評估比較浸潤口腔鱗狀上皮細胞癌組織中和周邊血液的淋巴細胞之表現自然殺手細胞受體分析…………………………………….64 第七章、 附圖…………………………………………………………65 附圖一、以圖表表示口腔麟狀上皮細胞的危險因子及關係…………65 附圖二、調節性T細胞經由腫瘤細胞召集、誘導、分化、增生之機制…66 | |
| dc.language.iso | zh-TW | |
| dc.subject | 腫瘤免疫編輯 | zh_TW |
| dc.subject | 調節性T淋巴球 | zh_TW |
| dc.subject | 腫瘤浸潤之淋巴球 | zh_TW |
| dc.subject | 口腔鱗狀細胞癌 | zh_TW |
| dc.subject | oral squamous cell carcinoma | en |
| dc.subject | cancer immune-editing | en |
| dc.subject | regulatory T lymphocytes | en |
| dc.subject | tumor-infiltrating lymphocyte | en |
| dc.title | 口腔鱗狀細胞癌中浸潤之調節性T淋巴球次群的表現與分析 | zh_TW |
| dc.title | Identification and characterization of regulatory T cell subsets infiltrated in human oral squamous cell carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李建國,許博欽,李正?,江伯倫 | |
| dc.subject.keyword | 腫瘤免疫編輯,口腔鱗狀細胞癌,腫瘤浸潤之淋巴球,調節性T淋巴球, | zh_TW |
| dc.subject.keyword | cancer immune-editing,oral squamous cell carcinoma,tumor-infiltrating lymphocyte,regulatory T lymphocytes, | en |
| dc.relation.page | 66 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| 顯示於系所單位： | 口腔生物科學研究所 | |
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