Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells
Kodama N, Komuta K, Sakai N, Nanba H.
Department of Microbial Chemistry, Kobe Pharmaceutical University
Natural killer (NK) cells are directly cytotoxic for tumor cells and play a primary role in regulating immune responses. We monitored levels of NK cell cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were maintained for one year. To elucidate the mechanisms underlying long-term activation of NK cells during treatment with D-Fraction, we examined tumor volume and levels of IFN-γ and TNF-α in MM46-bearing C3H/HeN mice to which D-Fraction was administered for 19 d. D-Fraction markedly suppressed tumor growth, corresponding with increases in TNF-α and IFN-α released from spleen cells and a significant increase in TNF-α expressed in NK cells. This suggests that the D-Fraction activates NK cells even on the 20th day after treatment. Furthermore, D-Fraction increased macrophage-derived interleukin (IL)-12, which serves to activate NK cells. These results suggest that NK cells are not only responsible for the early effects of D-Fraction on tumor growth, but also for the long-term tumor-suppressive effects of D-Fraction through increased IL-12 released from macrophages.