@article{oai:nagoya.repo.nii.ac.jp:02001651,
 author = {Miyajima, Noriyuki and Ragab Eissa, Ibrahim and Abdelmoneim, Mohamed and Naoe, Yoshinori and Ichinose, Toru and Matsumura, Shigeru and Bustos-Villalobos, Itzel and Mukoyama, Nobuaki and Morimoto, Daishi and Shibata, Masahiro and Takeuchi, Dai and Tsunoda, Nobuyuki and Kikumori, Toyone and Tanaka, Maki and Kodera, Yasuhiro and Kasuya, Hideki},
 issue = {4},
 journal = {Nagoya Journal of Medical Science},
 month = {Nov},
 note = {Canerpaturev (C-REV) is a highly attenuated, replication-competent, mutant strain of oncolytic herpes simplex virus type 1 that may be an effective new cancer treatment option. S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer. Although the antitumor effects of oncolytic viruses combined with 5-FU in vivo have been reported, the detailed mechanisms are unknown. Here, we investigated the antitumor mechanism of the combination of C-REV and S-1 in triple-negative breast cancer (TNBC) in the context of tumor immunity. The combined effect of C-REV and S-1 was evaluated in a bilateral tumor model of murine TNBC 4T1 in vivo. S-1 enhanced the TNBC growth inhibitory effects of C-REV, and decreased the number of tumor-infiltrating, myeloid-derived suppressor cells (MDSCs), which suppress both innate and adaptive immune responses. Moreover, C-REV alone and in combination with S-1 significantly increased the number of CD8+ T cells in the tumor and the production of interferon γ (IFNγ) from these cells. Our findings indicate that C-REV suppresses TNBC tumor growth by inducing the expansion of effector CD8+ T cell subsets in tumors in which S-1 can inhibit MDSC function. Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC.},
 pages = {683--696},
 title = {S-1 facilitates canerpaturev (C-REV)-induced antitumor efficacy in a triple-negative breast cancer model},
 volume = {83},
 year = {2021}
}