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Identification of an immunogenic neo-epitope encoded by mouse sarcoma using CXCR3 ligand mRNAs as sensors
http://hdl.handle.net/10076/00017678
http://hdl.handle.net/10076/00017678ea411a37-f9c1-46f8-9f9e-cc3fd9eb0650
名前 / ファイル | ライセンス | アクション |
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2017DM019 (1.9 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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公開日 | 2018-07-17 | |||||||||||
タイトル | ||||||||||||
タイトル | Identification of an immunogenic neo-epitope encoded by mouse sarcoma using CXCR3 ligand mRNAs as sensors | |||||||||||
言語 | en | |||||||||||
言語 | ||||||||||||
言語 | eng | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | Checkpoint blockade | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | CXCR3 ligands | |||||||||||
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言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | immune response | |||||||||||
キーワード | ||||||||||||
言語 | en | |||||||||||
主題Scheme | Other | |||||||||||
主題 | mutated antigen | |||||||||||
資源タイプ | ||||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
資源タイプ | doctoral thesis | |||||||||||
アクセス権 | ||||||||||||
アクセス権 | open access | |||||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
著者 |
藤井, 啓介
× 藤井, 啓介
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抄録 | ||||||||||||
内容記述タイプ | Abstract | |||||||||||
内容記述 | The CXCR3 ligands CXCL9, 10, and 11 play critical roles in the amplification of immune responses by recruiting CXCR3+ immune effector cells to the tumor site. Taking advantage of this property of CXCR3 ligands, we aimed to establish a novel approach to identify immunogenic mutated-antigens. We examined the feasibility of using CXCR3 ligand mRNAs as sensors for detection of specific immune responses in human and murine systems. We further investigated whether this approach is applicable for the identification of immunogenic mutated-antigens by using murine sarcoma lines. Rapid synthesis of CXCR3 ligand mRNAs occurred shortly after specific immune responses in both human and murine immune systems. Particularly, in CMS5 tumor-bearing mice, we detected specific immune responses to mutated mitogen-activated protein kinase 2 (ERK2), which has previously been identified as an immunogenic mutated-antigen. Furthermore, by combining this approach with whole-exome and transcriptome sequencing analyses, we identified an immunogenic neo-epitope derived from mutated staphylococcal nuclease domain-containing protein 1 (Snd1) in CMS7 tumor-bearing mice. Most importantly, we successfully detected the specific immune response to this neo-epitope even without co-administration of anti-cytotoxic T-lymphocyte protein-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-glucocorticoid-induced TNFR-related protein (GITR) antibodies, which vigorously augmented the immune response and consequently enabled us to detect the specific immune response to this neo-epitope by conventional IFNγ intracellular staining method.Our data indicate the potential usefulness of this strategy for the identification of immunogenic mutated-antigens. We propose that this approach would be of great help for the development of personalized cancer vaccine therapies in future. | |||||||||||
内容記述 | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | 本文 / Mie University Graduate School of Medicine | |||||||||||
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内容記述タイプ | Other | |||||||||||
内容記述 | 15p | |||||||||||
書誌情報 |
発行日 2018-03-26 |
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DOI | ||||||||||||
識別子タイプ | DOI | |||||||||||
関連識別子 | 10.1080/2162402X.2017.1306617 | |||||||||||
フォーマット | ||||||||||||
内容記述タイプ | Other | |||||||||||
内容記述 | application/pdf | |||||||||||
著者版フラグ | ||||||||||||
出版タイプ | VoR | |||||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
出版者 | ||||||||||||
出版者 | 三重大学 | |||||||||||
出版者(ヨミ) | ||||||||||||
値 | ミエダイガク | |||||||||||
学位名 | ||||||||||||
学位名 | 博士(医学) | |||||||||||
学位授与機関 | ||||||||||||
学位授与機関識別子Scheme | kakenhi | |||||||||||
学位授与機関識別子 | 14101 | |||||||||||
学位授与機関名 | 三重大学 | |||||||||||
学位授与年月日 | ||||||||||||
学位授与年月日 | 2018-03-26 | |||||||||||
学位授与番号 | ||||||||||||
学位授与番号 | 甲医学第1876号 | |||||||||||
ノート | ||||||||||||
値 | Oncoimmunology,2017,6(5):e1306617,ISSN:2162-4011に掲載 | |||||||||||
資源タイプ(三重大) | ||||||||||||
値 | Doctoral Dissertation / 博士論文 |