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腫瘍内疲弊CD8 T細胞におけるJunBの役割
https://doi.org/10.15102/0002000705
https://doi.org/10.15102/0002000705540599da-8c4b-47f7-b039-8f409cb0e42f
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WangKeFulltext.pdf (7.5 MB)
Download is available from 2025/11/3.
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WangKeExamAbstract.pdf (48 KB)
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WangKeSummary.pdf (93 KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2024-11-25 | |||||||
| タイトル | ||||||||
| タイトル | 腫瘍内疲弊CD8 T細胞におけるJunBの役割 | |||||||
| 言語 | ja | |||||||
| タイトル | ||||||||
| タイトル | The Role of JunB in Exhausted CD8 T Cell Populations in Tumors | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | T cell biology | Anti-tumor immune responses | |||||||
| 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 | |||||||
| ID登録 | ||||||||
| ID登録 | 10.15102/0002000705 | |||||||
| ID登録タイプ | JaLC | |||||||
| 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 (英) |
Wang, Ke
× Wang, Ke
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| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Precursor exhausted T (Tpex) cells are sustained in the lymph nodes and tumor tissues, giving rise to terminally exhausted T (Ttex) cells for tumor control. Moreover, they are responsible for enhanced anti-tumor responses in immune checkpoint therapy. However, the mechanism underlying the maintenance of Tpex cells remains largely unknown. In this study, using a B16 mouse melanoma model, I demonstrate that the AP-1 transcription factor JunB is essential for persistence of tumor-resident Tpex and Ttex cells. I found that expression of JunB is enhanced when Tpex cells adapt to tumor tissues. Junb-deficient CD8 T cells can differentiate into Tpex cells in the tumor draining lymph nodes (TdLNs), but they cannot accumulate in the tumor, thus failing to control tumor growth. Junbdeficient tumor-specific CD8 T cells in TdLNs or intra-tumoral Tpex cells with dTAGmediated JunB degradation impairs maintenance of Tpex phenotypes, including loss of Ly108, upon ex vivo stimulation with tumor-infiltrating dendritic cells. Moreover, dTAGmediated JunB degradation in intra-tumoral Ttex cells significantly reduces cell viability and ability to express effector molecules. Transcriptomic and chromatin landscape analyses revealed that JunB promotes chromatin accessibility and expression of Myb, which is critical for Tpex maintenance. Importantly, overexpression of JunB enhances antitumor CD8 T cell responses. These results suggest that JunB is required for adaptation of Tpex cells to tumor environment and maintain balance between Tpex and Ttex cells. These JunB functions might be a target to improve CD8 T cell-dependent cancer therapy. | |||||||
| 言語 | en | |||||||
| 口頭試問日 | ||||||||
| 値 | 2024-09-20 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2024-10-31 | |||||||
| 学位名 | ||||||||
| 学位名 | Doctor of Philosophy | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第168号 | |||||||
| 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 | 38005 | |||||||
| 学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
| 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 | |||||||
| 権利 | ||||||||
| 権利情報 | © 2024 The Author. | |||||||
| 開始ページ | 1 | |||||||
