Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, Washington 98109, USA.
Hailing
H
Lu
Yi
Y
Yang
Ekram
E
Gad
Cynthia A
CA
Wenner
Amy
A
Chang
Emily R
ER
Larson
Yushe
Y
Dang
Mark
M
Martzen
Leanna J
LJ
Standish
Mary L
ML
Disis
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D011509:Proteoglycans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000172:deficiency / Q000276:immunology
D000903:Antibiotics, Antineoplastic; D011509:Proteoglycans; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C010770:polysaccharide-K