Lycium barbarum Polysaccharides Enhance T-Cell Function by Inhibiting Programmed Death-Ligand 1 via Phosphoinositide-3-Kinase/Protein Kinase B Suppression in Bladder Cancer Cells

Abstract

Lycium barbarum is a boxthorn that produces the goji berries. L. barbarum polysaccharide is a water soluble bioactive component extracted from L. barbarum L. that has been shown to exert multiple pharmacological effects including antitumor effects. Herein, we have explored the mechanism underlying inhibition of tumor growth in J82 bearing bladder carcinoma by L. barbarum polysaccharides. The results of in vitro studies show that L. barbarum polysaccharide inhibited the expression of programmed death-ligand 1 protein, but not the gene transcription in bladder carcinoma cells. Also, L. barbarum polysaccharide decreased the level of phospho-protein kinase B/protein kinase B in cancer cells, and phosphoinositide- 3-kinase/protein kinase B pathway agonists reversed the inhibitory effect of L. barbarum polysaccharide on protein kinase B activation and programmed death-ligand 1 expression. Furthermore, when T cells and cancer cells were cultured together, treatments with either L. barbarum polysaccharide or antiprogrammed death-ligand 1 protein, enhanced T cell function including the expression of interferon-γ and interleukin-2 that were inhibited by phosphoinositide-3-kinase/protein kinase B pathway agonists. In conclusion, the results suggested that L. barbarum polysaccharide could inhibit programmed deathligand 1 expression via phosphoinositide-3-kinase/protein kinase B suppression of bladder cancer cells and further enhance the T-cell function in tumor microenvironment.