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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 賈景山 | |
| dc.contributor.author | Yu-Chih Ou | en |
| dc.contributor.author | 歐育志 | zh_TW |
| dc.date.accessioned | 2021-05-20T20:15:03Z | - |
| dc.date.available | 2014-09-15 | |
| dc.date.available | 2021-05-20T20:15:03Z | - |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-15 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/9262 | - |
| 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。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，免疫編輯(immune-editing)也被視為一個重要的因素，目前已經有研究指出調節性T細胞(Tregs)和表現抑制性B7分子的細胞對於腫瘤微環境的免疫抑制以及腫瘤生長都有貢獻。在本論文中發現口腔癌腫瘤組織抑制性B7-H1分子和調節性T細胞的表現相關性，接著分析口腔癌病人表現抑制性B7-H1分子的腫瘤浸潤調節性T細胞。研究發現腫瘤組織CD4+CD25+Foxp3+調節性T細胞有88.08%表現B7-H1，比起病人PBMC(64.71%)(p= 0.001)和正常人PBMC (73.78%) (p=0.04)都高出許多，並且發現腫瘤組織B7-H1+Foxp3+和Foxp3+細胞之百分比在TIL呈現中度相關(r=0.61)，而在CD4+ T細胞內則是呈現高度相關(r=0.75)。TIL內CD4+ CD25+Foxp3-活化T細胞之B7-H1接受體PD-1(programmed death-1)的平均表現螢光表現強度大約是PBMC的六倍高，CD4+CD25-Foxp3-未活化T細胞在TIL大約是PBMC的五倍高，然而CD4+CD25+Foxp3+調節性T在TIL大約只有PBMC的二倍高，並且發現B7-H1+Foxp3+表現百分比和PD-1表現強度在腫瘤組織CD4+T 細胞(r=0.6)具有中度相關性。此外在組織免疫染色也發現，口腔癌腫瘤組織中有Foxp3+ B7-H1+、Foxp3+ B7-H1-和PD-1+的浸潤T細胞。因此本論文發現有表現共同抑制性B7-H1分子的調節性T細胞亞群，浸潤於口腔鱗狀上皮細胞癌中，並且可能是藉由和PD-1的結合而具有免疫調節的功能。 | zh_TW |
| dc.description.abstract | Oral squamous cell carcinoma(OSCC) accounts for over 90% of the oral malignant neoplasms, ranks as the sixth major cause of cancer mortality rate in Taiwan and the incidence rate is raising. In addition to mutation of oncogene and gene toxicity, the cancer immune-editing is one of the important factors in human cancer currently.
The regulatory T cell and high levels of expression of coinhibitory B7 molecules are the mediators of immunosuppression in tumor microenviriment. Therefore, we investigated the relationship of B7-H1 and regulatory T cells in human oral squamous cell carcinoma.The results indicate that, in TIL, proportion of distinct CD25+ Foxp3+ cells in the CD4+ subset (88.08%) were enriched relative to that found in PBMC (64.71 %) from OSCC patients(p= 0.001)and PBMC(73.78%) from healthy donor (p=0.04).The linear correction analysis indicated that Foxp3+ and B7-H1+Foxp3+ Tregs were positively correlated in TIL(R=0.61) and CD4+ T cell(R=0.75). The PD-1 (the receptor of B7-H1) average expression on CD4+CD25-Foxp3- and CD4+CD25+ Foxp3- in TIL is five- or six-fold to PBMC , but it is only two fold in CD4+CD25+ Foxp3+ regulatory T cell. The linear analysis indicated that PD-1 average expression and proportion of B7-H1+Foxp3+ Tregs on CD4+T cell were positively correlated (R=0.60).Furthermore, we also observe the B7-H1+ Foxp3+Tregs and PD-1+ T cell in the immunohistochemistry. Therefore, B7-H1+Tregs and PD-1+ T cell infiltrated in tumor may play a immunoregulatory role in oral squamous cell carcinoma. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T20:15:03Z (GMT). No. of bitstreams: 1 ntu-98-R96450009-1.pdf: 1625833 bytes, checksum: cc72b09889d3cc4dda798e77909269b9 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 口試委員會審定書………………………………………………….………………1
致謝…………………………………………………………………….……………2 中文摘要………………………………………………………………..……………3 英文摘要…………………….………………………………………….……………4 目錄……………..……………………………………………………………………5 第一章、 緒論 第一節、研究背景 ㄧ、口腔鱗狀上皮細胞癌……………………………………….……………..9 二、口腔癌免疫抑制作用……………………………………………….……..11 三、調節性T細胞(regulatory T cells) ……………………………….……….12 四、抑制性B7分子(inhibitory B7 molecules) …………………….…………..15 第二節、研究動機與目的……………………………………………….……...20 第二章、 實驗分法與材料 第一節、檢體的收集及來源………………………………………….…………21 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………….…22 第三節、人類周邊血液單核球的分離與純化……………………….…………22 第四節、細胞表面染色…………………………………………….……………23 第五節、細胞內染色…………………………………………………….………23 第六節、腫瘤組織和正常組織之RNA萃取…………………….………………24 第七節、即時定量聚合酶連鎖反應(real-time PCR)………………….……..24 第八節、口腔癌組織及正常人組織的包埋和冷凍切片…………….…………24 第九節、組織免疫染色…………………………………….……………………25 第十節、反應性T細胞及調節性T細胞篩選分離方法及細胞增生和抑制試驗 ….……………………………………….……………………………….25 第十一節、周邊血液單核球與口腔鱗狀癌細胞株體外共同培養方法….….26 第三章、 結果 第一節、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤CD4+CD25+淋巴球，其 B7-H1共同抑制分子的細胞表現百分比和表現強度…………...……27 第二節、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤CD4+T細胞，B7-H1和Foxp3、CD25之表現有相關性……………………….….………...…27 第三節、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤CD4+Foxp3+調節性T細胞 表現較高比例且較高量的B7-H1，且B7-H1+Foxp3+細胞和Foxp3+細胞有相關性……………………………………………...…….…….…28 第四節、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤CD4+CD25+Foxp3+調節性T細胞表現較高比例且較高量的B7-H1………………….……..……29 第五節、口腔鱗狀細胞癌腫瘤組織CD4+CD25+Foxp3-和CD4+CD25-Foxp3-T細胞表現較高量的PD-1，且CD25+Foxp3+B7-H1+ T細胞和Foxp3-PD-1+ T細胞有相關性……………………………..................30 第六節、口腔鱗狀細胞癌細胞株SAS誘導CD4+CD25+細胞之B7-H1表現 .……………………………………………....31 第七節、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤B7-H1+CD4+CD25+ Foxp3+細胞表現較高比例且較高量的ICOS……….……….……....31 第八節、腫瘤組織表現較高量B7-H1、Foxp3、IL-10、IFN-γ、CD4、PD-1、 B7-DC和B7-H4之RNA，且Foxp3和B7-H1有相關性…….………....32 第九節、口腔鱗狀細胞癌病患分離出調節性T細胞具有抑制細胞增生的功 能….……………………...…………....……....................................…..32 第四章、 討論………………………………….…………………………..….…….34 第五章、 參考文獻……………………………………………..………..…….……38 第六章、 圖表 圖一、PBMC和TIL CD4+CD25+T細胞之B7-H1共同抑制分子細胞群體表現 百分比和平均細胞螢光表現強度……………………………...………..50 圖二、統計PBMC和TIL的CD4+CD25+T細胞之B7-H1共同抑制分子細胞 群體表現百分比和平均細胞螢光表現強度……………………… …....51 圖三、TIL CD4+CD25high、intermediate、low、negative T細胞之B7-H1共同 抑制分子細胞群體表現百分比和平均細胞螢光表現強度….…………52 圖四、PBMC和TIL CD4+Foxp3+ T細胞之B7-H1共同抑制分子細胞群體表 現百分比和平均細胞螢光表現強度……………………………….……53 圖五、統計PBMC和TIL CD4+Foxp3+ T細胞的B7-H1共同抑制分子細胞群 體表現百分比和平均細胞螢光表現強度…………………….…………54 圖六、腫瘤組織Foxp3+B7-H1+T細胞和Foxp3+T細胞的相關性……………55 圖七、PBMC和TIL的 CD4+CD25+Foxp3+、CD4+CD25+Foxp3-、 CD4+CD25-Foxp3- T細胞之B7-H1共同抑制分子細胞群體表現百分比 和平均細胞螢光表現強度…………………………………………….…..56 圖八、統計PBMC和TIL的 CD4+CD25+Foxp3+、CD4+CD25+Foxp3-、 CD4+CD25-Foxp3- T細胞之B7-H1共同抑制分子細胞群體表現百分比 和平均細胞螢光表現強度……………………………………………..….57 圖九、PBMC和TIL的CD4+CD25+Foxp3+、CD4+CD25+Foxp3-、 CD4+CD25-Foxp3- T細胞之PD-1共同抑制分子的細胞螢光表現強 度…………………………………………………………...………...…….58 圖十、腫瘤組織Foxp3+B7-H1+T細胞和PD-1 T細胞的相關性……….......…59 圖十一、口腔鱗狀細胞癌腫瘤組織經組織切片和免疫染色所見到的CD4+CD25+ Foxp3+B7-H1+調節性T細胞和PD-1浸潤細胞...............…60 圖十二、口腔鱗狀細胞癌細胞株SAS誘導CD4+CD25+T細胞之B7-H1表現……………………………………………………….…………….………61 圖十三、口腔鱗狀細胞癌病患分離出之腫瘤內浸潤CD4+Foxp3+細胞的B7-H1 和ICOS表現相關性…………………………………………….……..62 圖十四、在腫瘤組織RNA level B7-H1和相關分子的表現量以及其相關性 ……………………………………………………………….…………..63 圖十五、口腔鱗狀細胞癌病患之PBMC CD4+CD25hi細胞的細胞增生抑制試 驗……………………….……………………………………………..…64 附圖一、調節性T細胞免疫抑制機制…………………………………….…….65 附圖二、B7分子的表現和功能…………………………………….…….……...65 | |
| dc.language.iso | zh-TW | |
| dc.title | 探討口腔鱗狀上皮細胞癌中表現
B7-H1和PD-1之浸潤T淋巴球 | zh_TW |
| dc.title | Identification of B7-H1 and PD-1 expressing T cells
infiltrated in human oral squamous cell carcinoma | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許秉寧,李建國 | |
| dc.subject.keyword | 抑制性B7-H1分子,調節性T細胞,口腔鱗狀細胞癌,計畫性死亡-1, | zh_TW |
| dc.subject.keyword | B7-H1,regulatory T cells,oral squamous cell carcinoma,PD-1, | en |
| dc.relation.page | 65 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2009-07-15 | |
| dc.contributor.author-college | 牙醫專業學院 | 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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