| Item type |
文献 / Documents(1) |
| 公開日 |
2023-06-20 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1111/cas.15620 |
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関連名称 |
10.1111/cas.15620 |
| 出版タイプ |
|
|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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|
タイトル |
S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor |
| タイトル別表記 |
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その他のタイトル |
胸部腫瘍において、S-1は腫瘍由来Bv8およびS100A8の制御を介してMDSCを除去しPD-1阻害薬の効果を増強する |
| 著者 |
グエン, ナ チ
三橋, 惇志
荻野, 広和
香西, 博之
米田, 浩人
Afroj, Tania
佐藤, 正大
軒原, 浩
篠原, 勉
西岡, 安彦
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| 抄録 |
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内容記述 |
Myeloid-derived suppressor cells (MDSCs) have been known to play a pivotal role in the induction of immune tolerance, which limits the benefits of immune checkpoint inhibitors (ICIs). Recent studies revealed that several chemotherapeutic agents decreased tumor-infiltrating MDSCs. Therefore, combination therapy with cytotoxic chemotherapeutic agents and ICIs was approved for first-line treatment for lung cancer. However, the impact of chemotherapeutic agents on MDSCs and an optimal partner of ICIs has not been fully investigated in thoracic tumors, including lung cancer and malignant pleural mesothelioma. In the present study, we found that treatment with 5-FU and its oral formulation, S-1, suppressed tumor progression and inhibited the accumulation of MDSCs in thoracic tumor-bearing mice. Tumor-infiltrating T cells and dendritic cells were significantly expanded in S-1-treated mice. 5-FU suppressed the ability of tumor cells to recruit MDSCs, while it did not suppress the survival and differentiation of mouse MDSCs in vitro. We also revealed that 5-FU or S-1 significantly downregulated the expression of tumor-derived Bv8 and S100A8. The knockdown of Bv8 or S100A8 in tumor cells suppressed tumor growth and MDSC recruitment in vivo. Furthermore, in comparison with pemetrexed, administration of S-1 improved the synergistic therapeutic efficacy of anti-PD-1 antibodies with or without carboplatin. Our findings revealed a novel mechanism wherein S-1 primed a favorable tumor microenvironment to provide the rationale for combination therapy with S-1 and ICIs as the optimal therapy for thoracic cancer. |
| キーワード |
|
|
主題 |
oncology |
| キーワード |
|
|
主題 |
immune checkpoint inhibitor |
| キーワード |
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|
主題 |
myeloid-derived suppressor cells |
| キーワード |
|
|
主題 |
S-1 |
| キーワード |
|
|
主題 |
Bv8 |
| キーワード |
|
|
主題 |
S100A8 |
| 書誌情報 |
en : Cancer Science
巻 114,
号 2,
p. 384-398,
発行日 2022-10-26
|
| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
13497006 |
| 出版者 |
|
|
出版者 |
Japanese Cancer Association |
| 出版者 |
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|
出版者 |
John Wiley & Sons |
| 備考 |
|
|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Na T. Nguyen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。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, 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. |
| EID |
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識別子 |
396711 |
| 言語 |
|
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言語 |
eng |
| 報告番号 |
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|
学位授与番号 |
甲第3703号 |
| 学位記番号 |
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|
値 |
甲医第1573号 |
| 学位授与年月日 |
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学位授与年月日 |
2023-03-23 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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|
学位授与機関名 |
徳島大学 |
k3703_abstract.pdf (127 KB)
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