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Brachyury-targeted immunotherapy combined with gemcitabine against head and neck
https://asahikawa-med.repo.nii.ac.jp/records/2000327
https://asahikawa-med.repo.nii.ac.jp/records/2000327cb116567-d939-45a3-a3dd-d1246024c935
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
O501 Yamamoto Hidekiyo_TD.pdf (2.2 MB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||||
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| 公開日 | 2025-02-12 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Brachyury-targeted immunotherapy combined with gemcitabine against head and neck | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Brachyury | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Gemcitabine | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Head and neck squamous cell carcinoma | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Immunotherapy | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Peptide vaccine | |||||||||||
| キーワード | ||||||||||||
| 言語 | en | |||||||||||
| 主題Scheme | Other | |||||||||||
| 主題 | Tumor-associated 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 | |||||||||||
| その他（別言語等）のタイトル | ||||||||||||
| その他のタイトル | 頭頸部癌におけるBrachyury標的免疫療法とGemcitabineの併用療法に関する研究 | |||||||||||
| 言語 | ja | |||||||||||
| 著者 |
山本, 英聖
× 山本, 英聖
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| bibliographic_information |
en : Cancer Immunol Immunother 巻 72, 号 8, p. 2799-2812, 発行日 2023-08-01 |
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| ISSN | ||||||||||||
| 収録物識別子タイプ | PISSN | |||||||||||
| 収録物識別子 | 0340-7004 | |||||||||||
| DOI | ||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | https://doi.org/10.1007/s00262-023-03460-0 | |||||||||||
| 識別番号 その他 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | PMID:37173455 | |||||||||||
| 言語 | en | |||||||||||
| dissertation_number | ||||||||||||
| 学位授与番号 | 乙第501号 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2023-09-29 | |||||||||||
| 学位名 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位名 | 博士（医学） | |||||||||||
| item_10_degree_grantor_32 | ||||||||||||
| 言語 | ja | |||||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||||
| item_10_description_33 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4+ T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer. | |||||||||||
| 言語 | en | |||||||||||
| 出版タイプ | ||||||||||||
| 出版タイプ | VoR | |||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||
