Orally Administered Particulate β-Glucan Modulates Tumor-Capturing Dendritic Cells and Improves Antitumor T-Cell Responses in Cancer

• Published in: Clinical cancer research 2010-11, Vol.16 (21), p.5153-5164
• Main Authors: BING LI, YIHUA CAI, CHUNJIAN QI, HANSEN, Richard, CHUANLIN DING, MITCHELL, Thomas C, JUN YAN
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Oral; Animals; Antineoplastic agents; beta-Glucans - administration & dosage; Biological and medical sciences; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - pathology; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Dendritic Cells - physiology; Dosage Forms; Drug Evaluation, Preclinical; Immunity, Cellular - drug effects; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - pathology; Phagocytosis - drug effects; Pharmacology. Drug treatments; Powders; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-10-0820

The beneficial properties of β-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 β-glucan therapy has any effect on antitumor adaptive T-cell responses. We first examined the trafficking of orally administered particulate yeast-derived β-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 β-glucan therapy induces augmented T-cell responses. Lewis lung carcinoma and RAM-S lymphoma models were used to test oral β-glucan therapeutic effect. Further mechanistic studies including tumor-infiltrating T cells and cytokine profiles within the tumor milieu were determined. Orally administered particulate β-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-γ production of tumor-infiltrating T cells and CTL responses were significantly enhanced on β-glucan treatment, which ultimately resulted in significantly reduced tumor burden. Moreover, β-glucan-treated tumors had significantly more DC infiltration with the activated phenotype and significant levels of Th1-biased cytokines within the tumor microenvironment. These data highlight the ability of yeast-derived β-glucan to bridge innate and adaptive antitumor immunity and suggest that it can be used as an adjuvant for tumor immunotherapy.