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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 賈景山 | |
dc.contributor.author | Jung-Hsuan Ye | en |
dc.contributor.author | 葉容瑄 | zh_TW |
dc.date.accessioned | 2021-06-08T02:58:59Z | - |
dc.date.copyright | 2017-09-12 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-28 | |
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Thibult, M.L., et al., PD-1 is a novel regulator of human B-cell activation. Int Immunol, 2013. 25(2): p. 129-37. 54. Ren, Z., H. Peng, and Y.X. Fu, PD-1 Shapes B Cells as Evildoers in the Tumor Microenvironment. Cancer Discov, 2016. 6(5): p. 477-8. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20693 | - |
dc.description.abstract | α-烯醇酶被認為是腫瘤相關的抗原,已知在不同類型的癌症病患中,皆有對抗α-烯醇酶的自體抗體和T細胞,但目前對於這些T細胞的特徵並不是很清楚。除此之外,對抗鏈球菌表面α-烯醇酶的抗體,可以對人類自體的α-烯醇酶作用,可能是造成自體反應的重要因素,然而這樣的情況是否同樣出現在T細胞上是未知的。為了回答這些問題,我們利用細菌及人類專屬的α-烯醇酶胜肽群,各別去刺激正常人及口腔癌病人的週邊血液單核細胞。我們發現正常人的T細胞,也能對人類專屬的α-烯醇酶胜肽群產生反應,雖然有反應的比例比口腔癌病人低。在口腔癌病患中,腫瘤浸潤T細胞對α-烯醇酶胜肽群的反應與週邊血液T細胞不盡相同。而在有反應的人之中,相較於正常人,口腔癌病患對細菌及人類α-烯醇酶有反應的T細胞比例比較高。這些對α-烯醇酶有反應的T細胞,可能是初始T細胞、中心記憶T細胞、效應記憶T細胞及末端分化效應T細胞。在效應記憶T細胞及末端分化效應T細胞之中,大部份對α-烯醇酶有反應的T細胞都表現CD127和PD-1。因此,我們進一步探討PD-1阻斷對這些T細胞的影響。對細菌α-烯醇酶有反應的T細胞,在PD-1阻斷後可能增加或減少,然而對人類α-烯醇酶有反應的T細胞,在PD-1阻斷後只會減少。我們的結果顯示正常人與口腔癌病患對細菌或人類α-烯醇酶的反應不同,PD-1阻斷對這些T細胞的效應也不同。 | zh_TW |
dc.description.abstract | α-enolase has been known as a tumor-associated antigen, autoantibodies and T cells against α-enolase have been defined in several types of cancer patients. However, the characteristics of enolase-reactive T cells are poorly understood so far. Furthermore, it has been reported that antibodies target streptococcal surface enolase could react with human α-enolase, playing an important role in the initiation of auto-reactivity. However, whether TCR cross-reaction between bacterial and human enolase has not been verified. To address the questions, we used bacteria-specific and human-specific enolase peptides to stimulate peripheral blood mononuclear cells (PBMCs) of healthy donors and oral cancer patients. We reveal that healthy donors also respond to human enolase with lower proportion than oral cancer patients. In oral cancer patients, tumor-infiltrating lymphocytes (TILs) show different reactivity to enolase peptides from PBMCs. Among the responders, higher frequency of bacterial and human enolase-reactive CD8 T cells in oral cancer patients than healthy donors. Characterize the phenotype of enolase-reactive CD8 T cells, they may be naïve, central memory (TCM), effector memory (TEM), and terminally differentiated T cells (TEMRA). In TEM and TEMRA subsets, majority of enolase-reactive T cells are CD127+ and PD-1+. Therefore, We further explore the effects of PD-1 blockade on enolase-reactive T cells. Surprisingly, bacterial enolase-reactive T cells from different individuals show converse reactions to PD-1 blockade, while human enolase-reactive T cells among the responders only reduce the reactions after PD-1 blockade. Our results suggest the differential reactivities to bacterial or human enolase in healthy donors and oral cancer patients, and the different effects after PD-1 blockade on enolase-reactive CD8 T cells | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:58:59Z (GMT). No. of bitstreams: 1 ntu-106-R04449005-1.pdf: 5341891 bytes, checksum: 68abfa0146f6cb2a65b1fab74fc49d9d (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 誌謝 I
中文摘要 II Abstract III 目錄 v 圖目錄 vii Chapter 1. Introduction 1 1.1. Our previous studies about CD8 effector/memory subsets in oral squamous carcinoma patients 1 1.2. Our previous studies about adaptive immune response toward α-enolase in oral lichen planus patients and oral squamous carcinoma patients 2 1.3. Basic characteristics of human α-enolase 2 1.3.1. Basic characteristics of streptococcal surface α-enolase 3 1.3.2. Cross-reactivity between streptococcal surface enolase and human α-enolase 4 1.3.3. α-enolase as a tumor associated antigen 4 1.3.4. α-enolase and autoimmune diseases 6 1.4. Cancer immunology 6 1.4.1. Tumor associated antigen as target may encounter problem 7 1.4.2. CD8 T cells involved in tumor immune 8 1.4.3. Exhausted T cells 8 1.4.4. Immune checkpoint blockade 9 1.5. Effector memory CD8 T cells (TEM) 10 1.6. Terminally differentiated CD8 T cells (TEMRA) 11 1.7. CD127 on effector/memory T cells 12 1.8. Oral cancer 13 1.9. Oral lichen planus 14 Chapter 2. Purposes and Aims 16 Chapter 3. Materials and Methods 17 3.1. Human Subjects 17 3.2. Dissolved CMV peptides and α-enolase peptides 17 3.3. Isolation of peripheral blood mononuclear cells (PBMCs) 17 3.4. Isolation of tumor-infiltrating lymphocytes (TILs) 18 3.5. Peptide-specific T cells induction Assay 19 3.6. Flow cytometry analysis (FACS) 19 3.7. Cell sorting 20 3.8. Generation of moDCs from freshly isolated monocytes 21 3.9. Cell proliferation 22 3.10. Western blot Analysis 22 3.11. Immunohistochemistry staining 23 3.12. Statistical analysis 24 3.13. Antibodies for flow cytometry, PD-1 blockade, IHC, and WB 25 3.14. α-enolase peptide pools for T cells stimulation 26 Chapter 4. Result 27 4.1. α-enolase expressed on normal section and tumor mass 27 4.2. α-enolase-specific T cells were present in HD, OSCC, and OLP patients. 27 4.3. Most of α-enolase-specific T cells were CD127+ and PD-1+ 29 4.4. TILs showed differential reactivities to α-enolase compared to PBMCs 30 4.5. Utilizing moDCs as APC to induce α-enolase-specific T cells 30 4.6. Different effects of PD-1 blockade on α-enolase-specific T cells 31 4.7. Autoantibody intensity was not correlated with auto-reactive T cell response 33 Chapter 5. Discussion 34 Chapter 6. Reference 40 Chapter 7. Figures 46 | |
dc.language.iso | en | |
dc.title | 正常人與口腔癌病患中CD8+ T細胞亞群對細菌或自體α-烯醇酶的反應及PD-1阻斷後的效果 | zh_TW |
dc.title | Effects of PD-1 blockade on CD8+ T cell subsets with differential reactivities to bacterial or self-α-enolase in healthy donors and oral cancer patients | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 邱彥霖 | |
dc.contributor.oralexamcommittee | 李建國,顧家綺 | |
dc.subject.keyword | α-烯醇?,口腔癌,T細胞, | zh_TW |
dc.subject.keyword | α-enolase,oral cancer patients,T cells, | en |
dc.relation.page | 58 | |
dc.identifier.doi | 10.6342/NTU201702161 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-07-28 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 免疫學研究所 | zh_TW |
顯示於系所單位: | 免疫學研究所 |
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