Abstract 523: γα T cells are activated by protein-bound polysaccharide krestin (PSK) and contribute to the antitumor effect of PSK

Abstract

Abstract Gamma delta (γδ) T cells play an important role in anti-tumor immunity, and novel methods to augment γδ T cell function are highly desired. It has recently been shown that toll-like receptor (TLR) agonists may modulate the function of γδ T cells, so we questioned whether protein-bound polysaccharide krestin (PSK), a mushroom extract with TLR2 agonist activity, can activate γδ T cell. Using splenocytes from neu-transgenic mice, we found that γδ T cells produce IFN-γ after PSK treatment and have up-regulated expression of CD25 and CD69. The expression of CD107a in γδ T cells was also enhanced by PSK. To investigate whether the effect of PSK on γδ T cells is direct or indirect via activation of dendritic cells (DC), purified γδ T cells were cultured either alone or together with bone marrow derived DC (BMDC) in a co-culture or trans-well system and then stimulated with PSK. Results showed that direct cell-to-cell contact between γδ T cells and DC is required for optimal activation of γδ T cells. In the absence of DC, PSK can co-stimulate γδ T cells with anti-γδ TCR or anti-CD3 mAb. Oral administration of PSK in neu-transgenic mice with implanted breast tumors resulted in increased percentage of γδ T cells among splenocytes and increased expression of NKG2D on γδ T cells. Depleting γδ T cells during PSK treatment decreased the anti-tumor effect of PSK. All together, these results demonstrated that γδ T cells are activated by PSK and contribute to the anti-tumor effect of PSK. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 523. doi:1538-7445.AM2012-523