title: Efficacy of Juzentaihoto for Tumor Immunotherapy in B16 Melanoma Metastasis Model.
abstract: Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis.Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs. Additionally, we assessed NK cell activity in ex vivo experiments.Results. JTT significantly suppressed B16 cell metastasis, whereas injection of anti-asialo-GM1 antibody into mice abrogated the inhibitory actions of JTT. JTT significantly increased interleukin- (IL-) 12 and interferon- (IFN-)γlevels in serum and induced NK cell activity. It increased the inhibitory actions of the anti-PD-1 antibody on B16 cell metastasis.Discussion. These data suggest that JTT inhibits B16 cell metastasis by inducing NK cell activity. Additionally, combination therapy with JTT and anti-PD-1 antibody increased treatment response rates for B16 melanoma.
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Shintaro
authors.identifier: 0000-0002-6763-5583
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Tezuka
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Kazuhito
authors.identifier: 0000-0001-5168-472X
authors.initials: K
authors.lastname: Asano
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Masataka
authors.identifier: 0000-0001-7621-2024
authors.initials: M
authors.lastname: Sunagawa
authors.affiliation: Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Tadashi
authors.identifier: 0000-0002-2506-2844
authors.initials: T
authors.lastname: Hisamitsu