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マウス固形腫瘍に対するT細胞免疫療法における加齢の影響
https://doi.org/10.15102/0002000710
https://doi.org/10.15102/000200071087319727-b07d-4e74-819f-585c7a0d9843
| 名前 / ファイル | ライセンス | アクション |
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KadyrzhanovaGulfiyaFulltext.pdf (6.1 MB)
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KadyrzhanovaGulfiyaExamAbstract.pdf (48 KB)
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KadyrzhanovaGulfiyaSummary.pdf (84 KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
|---|---|---|---|---|---|---|---|---|
| 公開日 | 2024-12-03 | |||||||
| タイトル | ||||||||
| タイトル | マウス固形腫瘍に対するT細胞免疫療法における加齢の影響 | |||||||
| 言語 | ja | |||||||
| タイトル | ||||||||
| タイトル | Aging Effects on Murine Adoptive T cell Therapy for Solid Tumor | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | Anti-tumor cytotoxic CD8 T cell responses | adoptive T cell therapy | aging effects on T cells | |||||||
| 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 | 10.15102/0002000710 | |||||||
| 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) |
Kadyrzhanova, Gulfiya
× Kadyrzhanova, Gulfiya
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| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Aging is associated with reduction in diversity of antigen-specificity and activity of T cells. This might be related to an increased prevalence of cancers in people over 65 years old. Accordingly, adoptive T cell therapy (ACT) may be useful to treat cancers in elderly individuals, but the efficacy of ACT in elderly patients remains unclear. In this study, I found that intrinsic aging of CD8+ T cells impairs their anti-tumor activity in a mouse model of ACT with engineered T cells expressing TCR specific to tumor or antigens (TCR-T cells), although it does not affect cytotoxicity of CD8+ TCR-T cells in vitro. Single-cell RNA-sequencing (scRNA-seq) analysis revealed a significant increase in proportion of terminally exhausted cells and a decrease in progenitor exhausted cells in tumor-infiltrating aged TCR-T cells in ACT. Moreover, expression of endothelial PAS domain-containing protein 1 (Epas1) is significantly decreased in aged CD8+ T cells. Crispr-mediated ablation of Epas1 in young CD8+ T cells results in reduction in their anti-tumor activity and accumulation in the tumor in ACT. Moreover, Epas1-deficient tumor-infiltrating cells tend to exhibit the phenotype of terminally exhausted cells. These findings suggest that aging decreases Epas1 expression in CD8+ T cells, which in turn promotes cell exhaustion and decreases their anti-tumor activity. Enhancing Epas1 expression may therefore be a therapeutic strategy to improve the efficacy of ACT in the elderly. | |||||||
| 言語 | en | |||||||
| 口頭試問日 | ||||||||
| 値 | 2024-08-15 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2024-09-30 | |||||||
| 学位名 | ||||||||
| 学位名 | Doctor of Philosophy | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第166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. | |||||||
| 権利 | ||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||
| 権利情報 | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | |||||||
| 開始ページ | 1 | |||||||
