S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor

• Material Type: 博士論文
• Title: S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor
• Author/Editor: Nguyen, Na Thi; Mitsuhashi, Atsushi; Ogino, Hirokazu; Kozai, Hiroyuki; Yoneda, Hiroto; Afroj, Tania; Sato, Seidai; Nokihara, Hiroshi; Shinohara, Tsutomu; Nishioka, Yasuhiko
• Author Heading: Nguyen, Na Thi; Mitsuhashi, Atsushi; Ogino, Hirokazu; Kozai, Hiroyuki; Yoneda, Hiroto; Afroj, Tania; Sato, Seidai; Nokihara, Hiroshi; Shinohara, Tsutomu; Nishioka, Yasuhiko
• Publication, Distribution, etc.: Japanese Cancer Association|John Wiley & Sons
• Publication Date: 2022-10-26
• Publication Date (W3CDTF): 2022-10-26
• Alternative Title: 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
• Periodical title: Cancer Science
• No. or year of volume/issue: 114 2
• Volume: 114
• Issue: 2
• Pages: 384-398
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2023-03-23
• Dissertation Number: 甲第3703号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: oncology; immune checkpoint inhibitor; myeloid-derived suppressor cells; S-1; Bv8; S100A8
• Target Audience: 一般
• Note (General): 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.
• Access Restrictions: インターネット公開
• Rights (production): 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.
• Related Material (DOI): 10.1111/cas.15620
• Data Provider (Database): 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
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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