epiglucan and Lymphoma--B-Cell

β-glucans are polysaccharides that activate innate immunity. We herein investigated whether P-glucans promote the immunological effects of antibody drugs against malignant tumor cells using human peripheral blood mononuclear cells (PBMCs). Rituximab bound to CD20-specific lymphoma and exhibited cytotoxic activity in the presence of human mononuclear cells, but not neutrophils. The addition of Sparassis crispa (cauliflower mushroom)-derived β-glucan (SCG) and granulocyte macrophage colony-stimulating factor (GM-CSF) to co-cultures of PBMCs and Raji lymphoma cells further promoted antibody-dependent cell-mediated cytotoxicity (ADCC). The GM-CSF treatment increased β-glucan receptor expression on adherent cells in PBMCs. A co-stimulation with GM-CSF and SCG of PBMCs induced an increase in the number of spreading cells and the activation of natural killer (NK) cells. The enhancement in ADCC was abolished by the removal of NK cells, indicating that SCG and GM-CSF increased ADCC against lymphoma by activating β-glucan receptor-expressing cells in PBMCs and enhancing NK cell activity. The synergistic mechanisms of action of mushroom-derived β-glucans and biopharmaceuticals, including recombinant cytokines and antibodies, in the treatment of malignant tumor cells provide important insights into the clinical efficacy of β-glucans from mushrooms.

Topics: Agaricales; beta-Glucans; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Killer Cells, Natural; Leukocytes, Mononuclear; Lymphoma; Lymphoma, B-Cell

The aim of this study was to evaluate the effects of β-glucan on the expression of inflammatory mediators and metabolomic profile of oral cells [keratinocytes (OBA-9) and fibroblasts (HGF-1) in a dual-chamber model] infected by Aggregatibacter actinomycetemcomitans. The periodontopathogen was applied and allowed to cross the top layer of cells (OBA-9) to reach the bottom layer of cells (HGF-1) and induce the synthesis of immune factors and cytokines in the host cells. β-glucan (10 μg/mL or 20 μg/mL) were added, and the transcriptional factors and metabolites produced were quantified in the remaining cell layers and supernatant.. The relative expression of interleukin (IL)-1-α and IL-18 genes in HGF-1 decreased with 10 μg/mL or 20 μg/mL of β-glucan, where as the expression of PTGS-2 decreased only with 10 μg/mL. The expression of IL-1-α increased with 20 μg/mL and that of IL-18 increased with 10 μg/mL in OBA-9; the expression of BCL 2, EP 300, and PTGS-2 decreased with the higher dose of β-glucan. The production of the metabolite 4-aminobutyric acid presented lower concentrations under 20 μg/mL, whereas the concentrations of 2-deoxytetronic acid NIST and oxalic acid decreased at both concentrations used. Acetophenone, benzoic acid, and pinitol presented reduced concentrations only when treated with 10 μg/mL of β-glucan.. Treatment with β-glucans positively modulated the immune response and production of metabolites.

Topics: Acetophenones; Aggregatibacter actinomycetemcomitans; Anti-Infective Agents; Benzoic Acid; beta-Glucans; Cell Culture Techniques; Cell Line; Coculture Techniques; Cyclooxygenase 2; Cytokines; E1A-Associated p300 Protein; Fibroblasts; gamma-Aminobutyric Acid; Gene Expression; Host-Pathogen Interactions; Humans; Hydroxybutyrates; Immunomodulation; Inositol; Interleukin-18; Interleukin-1alpha; Keratinocytes; Lymphoma, B-Cell; Metabolome; Mouth; Oxalic Acid; Periodontal Diseases; Proto-Oncogene Proteins c-bcl-2; Real-Time Polymerase Chain Reaction

The knowledge of direct effects of β-glucans on tumor cells is limited. This study evaluated the impact of a soluble yeast-derived beta-(1-3),(1-6)-d-glucan, containing a fraction of aggregated sugar polymers, on viability, proliferation and expression of CD86 of the human B-cell lymphoma cell lines Daudi and Raji.. Proliferation of carboxyfluorescein diacetate succinimidyl ester (CFSE)-stained cell lines was determined by measuring depletion of the dye and cell death was quantified by staining with propidium iodide, both by flow cytometry. Surface expression of CD86 and the beta-glucan receptors dectin-1 and complement receptor 3 (CR3) was assessed by flow cytometry.. Exposure to the carbohydrate increased the expression of CD86 on both dectin-1(+)CR3(-) cell lines, whereas proliferation and viability of the cells were not affected.. Yeast-derived beta-glucan lacks cytotoxic effects towards B-lymphoma cells but up-regulation of CD86 suggests maturation of the cells via dectin-1 by the carbohydrate.

Topics: Animals; Antineoplastic Agents; B7-2 Antigen; beta-Glucans; Carbohydrates; Cell Line, Tumor; Cell Proliferation; Cell Survival; Fluoresceins; Gene Expression Regulation, Neoplastic; Humans; Lectins, C-Type; Lymphoma, B-Cell; Mice; Proteoglycans; Receptors, Immunologic; Saccharomyces cerevisiae; Succinimides; Up-Regulation

beta-glucans are biological response modifiers with activatory effects on macrophages, dendritic cells (DC), granulocytes and NK cells. In this study, we investigated the effect of a soluble yeast-derived beta-(1-3), (1-6)-D-glucan on prophylactic peptide vaccination against the B cell lymphoma A20 in syngeneic Balb/c mice. We found that repeated immunizations with two MHC class-I restricted peptides derived from the tumor antigen survivin combined with oral co-administration of beta-glucan could significantly diminish intradermal tumor growth, whereas peptide vaccination alone failed to control tumor growth. beta-glucan as single agent induced only a weak but non-significant growth inhibitory effect. To determine whether the tumor inhibitory effect of the combined treatment was associated with the induction of a tumor-specific immune response we quantified splenic DC and macrophages, analyzed the maturation of DC and measured the frequency of peptide-specific CD8+ and CD4+ T cells. Treated mice showed significantly increased numbers of splenic macrophages and mature DC compared to untreated tumor-bearing mice. After restimulation with both peptides in vitro elevated levels of interferon (IFN)-gamma-secreting CD8+ T cells were found in two of four tested mice following treatment and one of four mice showed a strong increase of interleukin (IL)-4-secreting CD4+ T cells. Our data reveal a beneficial effect of beta-(1-3), (1-6)-D-glucan in tumor growth inhibition by tumor-specific peptide vaccination which may rely on a function of the polymeric sugar as immunological adjuvant.

Topics: Administration, Oral; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Combined Modality Therapy; Female; Glucans; Immunity, Cellular; Inhibitor of Apoptosis Proteins; Lymphoma, B-Cell; Macrophages; Mice; Mice, Inbred BALB C; Microtubule-Associated Proteins; Repressor Proteins; Spleen; Survivin; Vaccination; Vaccines, Subunit