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Immune checkpoint inhibitors, including anti-programmed cell death 1 (anti-PD-1) antibodies, are novel promising forms of systemic immunotherapy. In the current study, we assessed whether gemcitabine (GEM) combined with anti-PD-1 antibody treatment was efficacious as immunochemotherapy for advanced PDAC using a murine model of liver metastasis. Methods The murine model of PDAC liver metastasis was established by intrasplenically injecting the murine pancreatic cancer cell line PAN02 into immunocompetent C57BL/6J mice. The mice were treated with an anti-PD-1 antibody, GEM, or a combination of GEM plus anti-PD-1 antibody, and compared with no treatment (control); liver metastases, immune cell infiltration, gene expression, immune cell response phenotypes, and overall survival were investigated. Results In the metastatic tumor tissues of mice treated with GEM plus anti-PD-1 antibody, we observed the increased infiltration of Th1 lymphocytes and M1 macrophages. Gene expression profile analysis of peripheral blood cells obtained from mice treated with GEM plus anti-PD-1 antibody clearly highlighted T cell and innate immune signaling pathways. Survival of PDAC liver metastasis mice was significantly prolonged by the combination therapy (median survival, 66 days) when compared with that of GEM alone treatment (median survival, 56 days). Expanded lymphocytes, which were isolated from the splenocytes of PDAC liver metastasis mice treated with GEM plus anti-PD-1 antibody, had an increased number of M1 macrophages. 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Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis
https://doi.org/10.24517/00065246
https://doi.org/10.24517/00065246bbb48b19-86ca-4135-896d-a58c2791204a
名前 / ファイル | ライセンス | アクション |
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ME-PR-SHIBA-K-e001367.pdf (6.1 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-01-27 | |||||
タイトル | ||||||
タイトル | Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
ID登録 | ||||||
ID登録 | 10.24517/00065246 | |||||
ID登録タイプ | JaLC | |||||
著者 |
Ho, Tuyen Thuy Bich
× Ho, Tuyen Thuy Bich× Nasti, Alessandro× Seki, Akihiro× Komura, Takuya× Inui, Hiiro× Kozaka, Takashi× Kitamura, Yoji× Shiba, Kazuhiro× Yamashita, Taro× Yamashita, Tatsuya× Mizukoshi, Eishiro× Kawaguchi, Kazunori× Wada, Takashi× Honda, Masao× Kaneko, Shuichi× Sakai, Yoshio |
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著者別表示 |
関, 晃裕
× 関, 晃裕× 小村, 卓也× 小阪, 孝史× 北村, 暘二× 柴, 和弘× 山下, 太郎× 水腰, 英四郎× 川口, 和紀× 和田, 隆志× 本多, 政夫× 金子, 周一× 酒井, 佳夫 |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学疾患モデル総合研究センター | |||||
書誌情報 |
Journal for ImmunoTherapy of Cancer 巻 8, 号 2, p. e001367, 発行日 2020 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2051-1426 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1136/jitc-2020-001367 | |||||
出版者 | ||||||
出版者 | BMJ Publishing Group | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background Pancreatic ductular adenocarcinoma (PDAC) is among the most dreadful of malignancies, in part due to the lack of efficacious chemotherapy. Immune checkpoint inhibitors, including anti-programmed cell death 1 (anti-PD-1) antibodies, are novel promising forms of systemic immunotherapy. In the current study, we assessed whether gemcitabine (GEM) combined with anti-PD-1 antibody treatment was efficacious as immunochemotherapy for advanced PDAC using a murine model of liver metastasis. Methods The murine model of PDAC liver metastasis was established by intrasplenically injecting the murine pancreatic cancer cell line PAN02 into immunocompetent C57BL/6J mice. The mice were treated with an anti-PD-1 antibody, GEM, or a combination of GEM plus anti-PD-1 antibody, and compared with no treatment (control); liver metastases, immune cell infiltration, gene expression, immune cell response phenotypes, and overall survival were investigated. Results In the metastatic tumor tissues of mice treated with GEM plus anti-PD-1 antibody, we observed the increased infiltration of Th1 lymphocytes and M1 macrophages. Gene expression profile analysis of peripheral blood cells obtained from mice treated with GEM plus anti-PD-1 antibody clearly highlighted T cell and innate immune signaling pathways. Survival of PDAC liver metastasis mice was significantly prolonged by the combination therapy (median survival, 66 days) when compared with that of GEM alone treatment (median survival, 56 days). Expanded lymphocytes, which were isolated from the splenocytes of PDAC liver metastasis mice treated with GEM plus anti-PD-1 antibody, had an increased number of M1 macrophages. Conclusion The combination of anti-PD-1 antibody immunotherapy with GEM was beneficial to treat a murine model of PDAC liver metastasis by enhancing the immune response mediated by Th1 lymphocytes and M1 macrophages and was associated with CD8+ T cells. © | |||||
権利 | ||||||
権利情報 | Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://jitc.bmj.com/ | |||||
関連名称 | https://jitc.bmj.com/ |