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Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma
https://asahikawa-med.repo.nii.ac.jp/records/5946
https://asahikawa-med.repo.nii.ac.jp/records/5946c3bace18-5528-49ba-87f7-4412721822b5
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
7066.pdf (108.2 kB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||
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| 公開日 | 2018-10-05 | |||||||||
| タイトル | ||||||||||
| タイトル | Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma | |||||||||
| 言語 | en | |||||||||
| 言語 | ||||||||||
| 言語 | jpn | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | CD4 T cell | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | epitope | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | head and neck squamous cell carcinoma | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | immunotherapy | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | p53 | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | phosphorylation | |||||||||
| キーワード | ||||||||||
| 主題Scheme | Other | |||||||||
| 主題 | post-translational modification | |||||||||
| 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 | |||||||||
| 著者 |
大原, 賢三
× 大原, 賢三
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| 著者 ローマ字 | ||||||||||
| Ohara, Kenzo | ||||||||||
| 書誌情報 |
Oncoimmunology 巻 7, 号 9, p. e1466771, 発行日 2018-08-01 |
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| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | 10.1080/2162402X.2018.1466771 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 10107A528 | |||||||||
| 学位名 | ||||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||
| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | The human T cell receptor is capable of distinguishing between normal and post-translationally modified peptides. Because aberrant phosphorylation of cellular proteins is a hallmark of malignant transformation, the expression of the phosphorylated epitope could be an ideal antigen to combat cancer without damaging normal tissues. p53 activates transcription factors to suppress tumors by upregulating growth arrest and apoptosis-related genes. In response to DNA damage, p53 is phosphorylated at multiple sites including Ser33 and Ser37. Here, we identified phosphorylated peptide epitopes from p53 that could elicit effective T helper responses. These epitope peptides, p5322-41/Phospho-S33 and p5322-41/Phospho-S37, induced T helper responses against tumor cells expressing the phosphorylated p53 protein. Moreover, chemotherapeutic agents augmented the responses of such CD4 T cells via upregulation of phosphorylated p53. The upregulation of phosphorylated p53 expression by chemotherapy was confirmed in in vitro and xenograft models. We evaluated phosphorylated p53 expression in the clinical samples of oropharyngeal squamous cell carcinoma and revealed that 13/24 cases (54%) were positive for phosphorylated p53. Importantly, the lymphocytes specific for the phosphorylated p53 peptide epitopes were observed in the head and neck squamous cell cancer (HNSCC) patients. These results reveal that a combination of phosphorylated p53 peptides and chemotherapy could be a novel immunologic approach to treat HNSCC patients. | |||||||||
| 資源タイプ | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
| フォーマット | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
