@article{oai:kanazawa-u.repo.nii.ac.jp:00058984,
 author = {関, 晃裕 and 小村, 卓也 and 小阪, 孝史 and 北村, 暘二 and 柴, 和弘 and 山下, 太郎 and 水腰, 英四郎 and 川口, 和紀 and 和田, 隆志 and 本多, 政夫 and 金子, 周一 and 酒井, 佳夫 and Ho, Tuyen Thuy Bich and Nasti, Alessandro and Seki, Akihiro and Komura, Takuya and Inui, Hiiro and Kozaka, Takashi and Kitamura, Yoji and Shiba, Kazuhiro and Yamashita, Taro and Yamashita, Tatsuya and Mizukoshi, Eishiro and Kawaguchi, Kazunori and Wada, Takashi and Honda, Masao and Kaneko, Shuichi and Sakai, Yoshio},
 issue = {2},
 journal = {Journal for ImmunoTherapy of Cancer},
 month = {},
 note = {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. ©, 金沢大学疾患モデル総合研究センター},
 title = {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},
 volume = {8},
 year = {2020}
}