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ID 119383
Title Alternative
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
Author
Kozai, Hiroyuki Tokushima University
Nguyen, Na Thi Tokushima University
Tsukazaki, Yuki Tokushima University
Yabuki, Yohei Tokushima University
Yoneda, Hiroto Tokushima University
Nokihara, Hiroshi Tokushima University|Center Hospital of the National Center for Global Health and Medicine
Keywords
5-fluorouracil
cancer immunotherapy
fluoropyrimidine
immunogenic cell death
thoracic malignancy
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Thoracic Cancer
ISSN
17597714
17597706
Publisher
China Lung Oncology Group|John Wiley & Sons Australia
Volume
15
Issue
5
Start Page
369
End Page
378
Published Date
2023-12-26
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3830号
Diploma Number
甲医第1608号
Granted Date
2024-04-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences