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ID 119383
タイトル別表記
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
著者
香西, 博之 徳島大学大学院医学研究科(医学専攻)
Nguyen, Na Thi Tokushima University
塚﨑, 佑貴 Tokushima University
Yabuki, Yohei Tokushima University
米田, 浩人 Tokushima University
軒原, 浩 Tokushima University|Center Hospital of the National Center for Global Health and Medicine
キーワード
5-fluorouracil
cancer immunotherapy
fluoropyrimidine
immunogenic cell death
thoracic malignancy
資料タイプ
学位論文
抄録
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.
掲載誌名
Thoracic Cancer
ISSN
17597714
17597706
出版者
China Lung Oncology Group|John Wiley & Sons Australia
15
5
開始ページ
369
終了ページ
378
発行日
2023-12-26
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Hiroyuki Kozaiの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3830号
学位記番号
甲医第1608号
学位授与年月日
2024-04-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系