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암 환경에서 IL-21에 의한 자연 살해 세포의 기능 저하 회복에 관한 연구 : Studies on Interleukin-21 mediated reversal of natural killer cell exhaustion in tumor microenvironment
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | 강창율 | - |
dc.contributor.author | 서형석 | - |
dc.date.accessioned | 2017-10-27T17:02:37Z | - |
dc.date.available | 2017-10-27T17:02:37Z | - |
dc.date.issued | 2017-08 | - |
dc.identifier.other | 000000144962 | - |
dc.identifier.uri | https://hdl.handle.net/10371/137037 | - |
dc.description | 학위논문 (박사)-- 서울대학교 융합과학기술대학원 분자의학 및 바이오제약학과, 2017. 8. 강창율. | - |
dc.description.abstract | During cancer immunoediting, tumor cells with spontaneous loss of Major Histocompatibility Complex (MHC) class I expression tend to gradually increase in the tumor microenvironment by preferentially escaping from immune surveillance of cytotoxic T cells even though MHC class I-deficient tumors have been historically considered to be susceptible to NK cell-dependent cytotoxicity. Recent studies demonstrated that most NK cells found in the tumor microenvironment of advanced cancers are defective, releasing the malignant MHC class I-deficient tumors from NK cell-dependent immune control. Here, I showed that an NKT cell-ligand loaded tumor-antigen expressing APC (Antigen Presenting Cell)-based vaccine effectively eradicated these advanced tumors that are not curable with a single immunotherapy. In this process, I found that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumors and that MHC class I downregulation in tumors was closely associated with the induction of NK cell exhaustion in tumor-bearing mice as well as in cancer patients. Furthermore, the recovery of NK cell function by IL-21 was critical for the anti-tumor effect of the vaccine against these advanced tumors. These results reveal the process involved in the induction of NK-cell dysfunction in advanced cancers and provide a guidance for the development of strategies for cancer immunotherapy. | - |
dc.description.tableofcontents | Introduction 1
Materials and Methods 10 Results 17 Discussion 63 Summary 67 References 68 | - |
dc.format | application/pdf | - |
dc.format.extent | 6079422 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 융합과학기술대학원 | - |
dc.subject | NK cell | - |
dc.subject | Exhaustion | - |
dc.subject | Cancer Immunotherapy | - |
dc.subject | Immune checkpoint | - |
dc.subject | IL-21 | - |
dc.subject | MHC class I | - |
dc.subject.ddc | 610.28 | - |
dc.title | 암 환경에서 IL-21에 의한 자연 살해 세포의 기능 저하 회복에 관한 연구 | - |
dc.title.alternative | Studies on Interleukin-21 mediated reversal of natural killer cell exhaustion in tumor microenvironment | - |
dc.type | Thesis | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 융합과학기술대학원 분자의학 및 바이오제약학과 | - |
dc.date.awarded | 2017-08 | - |
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