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Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy
http://hdl.handle.net/10191/35556
http://hdl.handle.net/10191/35556d5134c5a-1224-4c4f-95d5-9efe147813e5
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本文 (2.3 MB)
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要旨 (163.3 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2015-12-14 | |||||
| タイトル | ||||||
| タイトル | Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy | |||||
| タイトル | ||||||
| タイトル | Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 抗癌剤を用いたリンパ球除去後の抗腫瘍免疫における、抗癌剤耐性エフェクターおよび制御性T cellsの重要な役割 | |||||
| 著者 |
Saida, Yu
× Saida, Yu |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 50652 | |||||
| 姓名 | 才田, 優 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Antitumor immunity is augmented by cytotoxic lymphodepletion therapies. Adoptively transferred naive and effector T cells proliferate extensively and show enhanced antitumor effects in lymphopenic recipients. Although the impact of lymphodepletion on transferred donor T cells has been well evaluated, its influence on recipient T cells is largely unknown. The current study demonstrates that both regulatory T cells (Tregs) and effector CD8^+ T cells from lymphopenic recipients play critical roles in the development of antitumor immunity after lymphodepletion. Cyclophosphamide (CPA) treatment depleted lymphocytes more efficiently than other cytotoxic agents; however, the percentage of CD4^+CD25^+ Forkhead box P3^+ Tregs was significantly increased in CPA-treated lymphopenic mice. Depletion of these chemoresistant Tregs following CPA treatment and transfer of naive CD4^+ T cells augmented the antitumor immunity and significantly suppressed tumor progression. Further analyses revealed that recipient CD8^+ T cells were responsible for this augmentation. Using Rag2^<-/-> mice or depletion of recipient CD8^+ T cells after CPA treatment abrogated the augmentation of antitumor effects in CPA-treated reconstituted mice. The transfer of donor CD4^+ T cells enhanced the proliferation of CD8^+ T cells and the priming of tumor-specific CD8^+ T cells originating from the lymphopenic recipients. These results highlight the importance of the recipient cells surviving cytotoxic regimens in cancer immunotherapies. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 学位の種類: 博士（医学）. 報告番号: 甲第4064号. 学位記番号: 新大院博（医）甲第653号. 学位授与年月日: 平成27年9月24日 | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | The Journal of Immunology. 2015, 195(2), 726-735. | |||||
| 書誌情報 | 発行日 2015-09-24 | |||||
| 出版者 | ||||||
| 出版者 | 新潟大学 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.4049/jimmunol.1401468 | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2015-09-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4064号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博（医）甲第653号 | |||||
