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

• Material Type: 博士論文
• Title: Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: China Lung Oncology Group|John Wiley & Sons Australia
• Publication Date: 2023-12-26; 15 5
• Publication Date (W3CDTF): 2023-12-26
• Alternative Title: 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
• Degree grantor/type: 徳島大学
• Date Granted: 2024-04-25
• Date Granted (W3CDTF): 2024-04-25
• Dissertation Number: 甲第3830号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: 5-fluorouracil; cancer immunotherapy; fluoropyrimidine; immunogenic cell death; thoracic malignancy
• Target Audience: 一般
• Note (General): 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.
• Persistent ID (NDL): info:ndljp/pid/13722834; https://dl.ndl.go.jp/pid/13722834
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• Date Accepted (W3CDTF): 2024-07-05T22:07:00+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/119383
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