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-) γ levels 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.
Highlights
Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence
B16 cells were added to natural killer (NK) cells at a ratio of 1 : 20 (B16/NK), and supernatants were collected after coculture for 24 h [21] and stored at −80∘C until use for enzyme-linked immunosorbent assay (ELISA) measurements of IFN-γ concentrations
To determine the influence of NK cell inhibition on tumor cell metastasis, mice were treated with anti-asialo-GM1 antibody and intravenous injections of B16 cells
Summary
Melanoma affects 12 people per 100,000 and causes 600 deaths per year in Japan [1]. In Japan, clinicians who have studied both Western and Kampo medicines treat cancer patients with combinations of these medical interventions, and increasing numbers of cancer patients receive outpatient chemotherapy. Recent studies show that several tumors, including melanoma, have developed the ability to abolish T cell activation and prevent effective T cell antitumor. Checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) antibody, normally promote antitumor immunity by blocking this key negative regulator of T cell activation [15]. We examined the effects of JTT on NK cell activity and metastasis following combined treatment with anti-PD-1 antibody in a B16 transplantation model of metastasis
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