Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer.

Clinical Cancer Research

PubMedID: 20855461

Li B, Cai Y, Qi C, Hansen R, Ding C, Mitchell TC, Yan J. Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer. Clin Cancer Res. 2010;16(21):5153-64.
PURPOSE
The beneficial properties of ß-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 for eliciting complement receptor 3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether ß-glucan therapy has any effect on antitumor adaptive T-cell responses.

EXPERIMENTAL DESIGN
We first examined the trafficking of orally administered particulate yeast-derived ß-glucan and its interaction with dendritic cells (DC) that captured tumor materials. Antigen-specific T cells were adoptively transferred into recipient mice to determine whether oral ß-glucan therapy induces augmented T-cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral ß-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined.

RESULTS
Orally administered particulate ß-glucan trafficked into spleen and lymph nodes and activated DCs that captured dying tumor cells in vivo, leading to the expansion and activation of antigen-specific CD4 and CD8 T cells. In addition, IFN-? production of tumor-infiltrating T cells and CTL responses were significantly enhanced on ß-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, ß-glucan-treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment.

CONCLUSIONS
These data highlight the ability of yeast-derived ß-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.