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
• Degree grantor/type: 徳島大学
• Date Granted: 2023-03-23
• Date Granted (W3CDTF): 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.
• Persistent ID (NDL): info:ndljp/pid/12911864; https://dl.ndl.go.jp/pid/12911864
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-07-08T03:42:33+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/118295
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp