Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies

• 資料種別: 博士論文
• タイトル: Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies
• 著者・編者: Kozai, Hiroyuki; Ogino, Hirokazu; Mitsuhashi, Atsushi; Nguyen, Na Thi; Tsukazaki, Yuki; Yabuki, Yohei; Ozaki, Ryohiko; Yoneda, Hiroto; Sato, Seidai; Hanibuchi, Masaki; Shinohara, Tsutomu; Nokihara, Hiroshi; Nishioka, Yasuhiko
• 著者標目: Kozai, Hiroyuki; Ogino, Hirokazu; Mitsuhashi, Atsushi; Nguyen, Na Thi; Tsukazaki, Yuki; Yabuki, Yohei; Ozaki, Ryohiko; Yoneda, Hiroto; Sato, Seidai; Hanibuchi, Masaki; Shinohara, Tsutomu; Nokihara, Hiroshi; Nishioka, Yasuhiko
• 出版事項: China Lung Oncology Group|John Wiley & Sons Australia
• 出版年月日等: 2023-12-26
• 出版年（W3CDTF）: 2023-12-26
• 並列タイトル等: フッ化ピリミジンは、胸部悪性腫瘍の免疫原性細胞死を誘導することで、免疫チェックポイント阻害薬の免疫学的な至適パートナーとなり得る
• タイトル（掲載誌）: Thoracic Cancer
• 巻号年月日等（掲載誌）: 15 5
• 掲載巻: 15
• 掲載号: 5
• 掲載ページ: 369-378
• ISSN（掲載誌）: ISSN : 1759-7714; ISSN : 1759-7706
• 授与機関名: 徳島大学
• 授与年月日: 2024-04-25
• 報告番号: 甲第3830号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: 5-fluorouracil; cancer immunotherapy; fluoropyrimidine; immunogenic cell death; thoracic malignancy
• 対象利用者: 一般
• 一般注記: Background: Immune checkpoint inhibitors (ICIs) are a revolutionary paradigm in the treatment of thoracic malignancies and chemoimmunotherapy is a current standard care in this field. Chemotherapeutic agents are known to induce not only direct cytotoxic effects on tumor cells but also immune modulating effects, such as stimulating immunogenic cell death (ICD). Currently, either pemetrexed (PEM) or taxane plus platinum are combined with ICIs for patients with non-small cell lung cancer (NSCLC); however, it is still unknown whether these agents are immunologically optimal partners for ICIs. Methods: To determine the immunologically optimal chemotherapeutic agent, we first evaluated the ability of several chemotherapeutic agents, including platinum, PEM, taxane, and 5-fluorouracil (5-FU) to induce ICD using several thoracic tumor cell lines in vitro. ICD was evaluated by the cell surface expression of calreticulin (CRT) and adenosine-triphosphate (ATP) secretion. We further performed an antitumor vaccination assay in vivo. Results: 5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3+CD8+ T cells into the tumor microenvironment. Conclusion: Our findings indicate that fluoropyrimidine can be an immunologically optimal partner of ICIs through the induction of ICD for thoracic malignancies.
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• 関連情報（DOI）: 10.1111/1759-7714.15200
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/119383/20240523111956571935/k3830_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/119383/20240523111956662217/k3830_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/119383/20240523111956901667/k3830_fulltext.pdf fulltext