Japanese Kampo medicine ninjin'yoeito synergistically enhances tumor vaccine effects mediated by CD8(+) T cells

Although Japanese traditional herbal medicine (Kampo) has been widely applied to the treatment of various diseases, including cancer, their mechanisms of action have not yet been elucidated in detail, particularly regarding their role in tumor immunology. The present study investigated the antitumor effects of the Japanese Kampo medicine, ninjin'yoeito (NYT; Ren-Shen-Yang-Rong-Tang in Chinese), which was orally administered with or without an irradiated tumor cell vaccine to a subcutaneous CT26 colon carcinoma tumor model. The irradiated tumor cell vaccine in a prophylactic setting significantly delayed tumor growth in mice fed a control diet, whereas a diet containing NYT alone did not exert any antitumor effects in vivo. However, the inhibition of tumor growth was significantly greater in vaccinated mice fed the NYT diet compared with in vaccinated mice given the control diet. These results suggest that NYT synergistically enhances the effects of the antitumor vaccine. The depletion of cluster of differentiation (CD)8(+) T cells abrogated these effects, indicating that antitumor activity required CD8(+) T cells. Furthermore, reductions in CD4(+) CD25(+) and forkhead box protein 3(+) T regulatory cell numbers were more apparent between vaccinated mice fed the NYT diet and non-vaccinated mice fed the control diet than between vaccinated mice and non-vaccinated mice fed the control diet, suggesting that the weaker impact of T regulatory cells contributes to the augmentation of antitumor immunity by CD8(+) T cells in vaccinated mice fed with NYT. Overall, these results indicate that NYT synergistically enhances the effects of the prophylactic tumor vaccine mediated by CD8(+) T cells and that this Japanese Kampo medicine has potential as a useful adjuvant agent for cancer immunotherapy.