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Modulation of innate immune cell activation and function by Polysaccharide Krestin (PSK)
Anti-tumor effects of PSK, an extract from the fungal species Trametes versicolor, are reportedly mediated through both innate and adaptive (T cell dependent) anti-tumor immune response pathways. However, the mechanisms by which PSK modulates innate immune cells involved in the induction of antitumor immunity are unknown. Two groups of innate immune cells, accessory cells (monocytes and dendritic cells) and natural killer (NK) cells, are critical in priming T cell dependent, antitumor immune responses. Further, NK cells and dendritic cells cross-activate each other as a key initial event in priming adaptive immunity. This in vitro study using healthy human immune cells addressed the hypothesis that PSK immunopotentiates anti-tumor responses by enhancing activation and function of accessory and NK cells. We found that PSK induces expression of activation and differentiation markers CD80 and CD86 on monocytes, and augments their phagocytic capacity. PSK also dose-dependently enhances activation markers CD69 and CD25 on human primary NK cells. NK cell cytotoxicity of human PBMC against K562 tumor target cells is also dose-dependently increased by PSK pre-treatment. NK cells treated with PSK secrete a higher level of IFN-gamma, and more IFN-gamma expressing NK cells are observed, in response to IL-12 and IL-18, suggesting that PSK sensitizes NK cells to respond to these accessory cell-derived monokines. Further, NK cells cultured in the presence of PSK-treated, monocyte-derived dendritic cells proliferate significantly more than controls. These results suggest that PSK enhances activation, function and cross-talk between accessory cells and NK cells and may immunopotentiate antitumor responses through these mechanisms.
Acknowledgement: National Center for Complementary and Alternative Medicine (NCCAM)/NIH, funding agency.