Anti-Tumor Actions of Trametes Versicolor Extract Polysaccharide K Include Activation of Dendritic Cells and Gamma Delta T Cells

Polysaccharide K (PSK) is a mushroom extract with anti-tumor and immunomodulatory effects shown pre-clinically and clinically. We have shown that PSK can activate TLR2 and enhance NK cell function. This study examined the effect of PSK on APCs and gamma delta ((γ(δ) T cells. PSK enhanced TNF production in human THP-1 monocytic cells. PSK treatment induced IFN-(γ and upregulated expression of CD25, CD69 and CD107a in mouse splenocyte-derived (γ(δ T cells. To investigate whether PSK's effects were direct, purified (γ(δ T cells were cultured alone or with bone marrow derived DC in co-culture or trans-well system and stimulated with PSK. Direct cell-to-cell contact between (γ(δ T cells and DC was required for optimal (γ(δ T cell activation. Reciprocal activation of DC by PSK-activated (γ(δ T cells also occurred; PSK increased DC costimulatory molecule and IL-12 expression in the presence of (γ(δ T cells. PSK also co-stimulated anti-TCR and anti-CD3-stimulated (γ(δ T cells without DC. In vivo treatment with PSK activated (γ(δ T cells in tumor infiltrating lymphocytes. Depleting (γ(δ T cells during PSK treatment attenuated PSK's anti-tumor effects. Thus, PSK-induced activation of (γ(δ T cells and APCs contributes to the anti-tumor effects of PSK. These data, together with our previous findings on the effect of PSK on NK and CD8⁺ T cells, demonstrate that the effect of PSK on immune activation is multi-faceted, and activation of TLR2 on APCs leads to the subsequent activation of different effector cells (NK cells, CD8⁺ T cells and (γ(δ T cells) that contribute to the anti-tumor effects of PSK.