Polysaccharide Krestin Is a Novel TLR2 Agonist that Mediates Inhibition of Tumor Growth via Stimulation of CD8 T Cells and NK Cells
- 1 January 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 17 (1), 67-76
- https://doi.org/10.1158/1078-0432.ccr-10-1763
Abstract
Purpose: Polysaccharide krestin (PSK) is a mushroom extract that has been long used in Asia and recently in Western countries as a treatment for cancer due to its presumed immune potentiating effects. Although there have been reports of clinical responses after patients have ingested PSK, the mechanism of action of the agent remains undefined. The current study was undertaken to investigate the mechanism of the antitumor actions of PSK. Experimental Design: The immunostimulatory effect of PSK was first evaluated in vitro using splenocytes from neu transgenic mice and Toll-like receptor (TLR) 2 knockout (TLR2−/−) mice. Then the immunostimualtory and antitumor effect of PSK was determined using tumor-bearing neu transgenic mice, TLR2−/−, and wild-type C57BL/6 mice. Results: We demonstrate that PSK is a selective TLR2 agonist, and the activation of dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK in neu transgenic mice significantly inhibits breast cancer growth. Selective depletion of specific cell populations suggests that the antitumor effect of PSK is dependent on both CD8+ T cell and NK cells, but not CD4+ T cells. PSK does not inhibit tumor growth in TLR2−/− mice suggesting that the antitumor effect is mediated by TLR2. Conclusion: These results demonstrate that PSK, a natural product commonly used for the treatment of cancer, is a specific TLR2 agonist and has potent antitumor effects via stimulation of both innate and adaptive immune pathways. Clin Cancer Res; 17(1); 67–76. ©2010 AACR.Keywords
Other Versions
This publication has 51 references indexed in Scilit:
- Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in miceJCI Insight, 2010
- Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environmentsBlood, 2009
- Toll-like receptors and cancerNature Reviews Cancer, 2008
- Insulin-like Growth Factor–Binding Protein-2 Is a Target for the Immunomodulation of Breast CancerCancer Research, 2008
- Engagement of Toll‐like receptor‐2 on cytotoxic T‐lymphocytes occursin vivoand augments antitumor activityThe FASEB Journal, 2008
- TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenograftsProceedings of the National Academy of Sciences, 2007
- Dendritic Cells Prime Natural Killer Cells by trans-Presenting Interleukin 15Immunity, 2007
- Immunobiology of Toll‐like receptors: Emerging trendsImmunology & Cell Biology, 2006
- Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptorsJCI Insight, 2006
- Toll-like receptor 2 signaling modulates the functions of CD4+CD25+regulatory T cellsProceedings of the National Academy of Sciences, 2006