Cancer Immunology, Immunotherapy

, Volume 62, Issue 8, pp 1335–1345

Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK

  • Carol Inatsuka
  • Yi Yang
  • Ekram Gad
  • Lauren Rastetter
  • Mary L. Disis
  • Hailing Lu
Original Article

DOI: 10.1007/s00262-013-1436-4

Cite this article as:
Inatsuka, C., Yang, Y., Gad, E. et al. Cancer Immunol Immunother (2013) 62: 1335. doi:10.1007/s00262-013-1436-4

Abstract

Polysaccharide K (PSK) is a widely used mushroom extract that has shown anti-tumor and immunomodulatory effects in both preclinical and clinical studies. Therefore, it is important to understand the mechanism of actions of PSK. We recently reported that PSK can activate toll-like receptor 2 and enhances the function of NK cells. The current study was undertaken to study the effect of PSK on gamma delta (γδ) T cells, another important arm of the innate immunity. In vitro experiments using mouse splenocytes showed that γδ T cells produce IFN-γ after treatment with PSK and have up-regulated expression of CD25, CD69, and CD107a. To investigate whether the effect of PSK on γδ T cells is direct or indirect, purified γδ T cells were cultured either alone or together with bone marrow-derived DC 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. There was also reciprocal activation of DC by PSK-activated γδ T cells, as demonstrated by higher expression of costimulatory molecules and enhanced production of IL-12 by DC in the presence of γδ T cells. PSK can also co-stimulate γδ T cells with anti-TCR and anti-CD3 stimulation, in the absence of DC. Finally, in vivo treatment with PSK activates γδ T cells among the tumor infiltrating lymphocytes, and depleting γδ T cells during PSK treatment attenuated 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.

Keywords

PSK Polysaccharide γδ T cells TLR Breast cancer Innate immunity

Abbreviation

CAM

Complementary and alternative medicine

CTL

Cytotoxic T lymphocyte

DC

Dendritic cells

ELISA

Enzyme-linked immunosorbent assay

FBS

Fetal bovine serum

γδ

Gamma delta

IFN-γ

Interferon gamma

IL

Interleukin

mAb

Monoclonal antibody

NK

Natural killer

PAMP

Pathogen-associated molecular patterns

PBMC

Peripheral blood mononuclear cells

PBS

Phosphate-buffered saline

PSK

Polysaccharide K

TIL

Tumor infiltrating lymphocytes

TLR

Toll-like receptor

TNF-α

Tumor necrosis factor alpha

Supplementary material

262_2013_1436_MOESM1_ESM.pdf (101 kb)
Supplementary material 1 (PDF 101 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Carol Inatsuka
    • 1
  • Yi Yang
    • 1
  • Ekram Gad
    • 1
  • Lauren Rastetter
    • 1
  • Mary L. Disis
    • 1
  • Hailing Lu
    • 1
  1. 1.Tumor Vaccine Group, Center for Translational Medicine in Women’s HealthUniversity of WashingtonSeattleUSA