epiglucan and Cell-Transformation--Neoplastic

Our studies showed that tumor-infiltrating dendritic cells (DC) in breast cancer drive inflammatory Th2 (iTh2) cells and protumor inflammation. Here, we show that intratumoral delivery of the β-glucan curdlan, a ligand of dectin-1, blocks the generation of iTh2 cells and prevents breast cancer progression in vivo. Curdlan reprograms tumor-infiltrating DCs via the ligation of dectin-1, enabling the DCs to become resistant to cancer-derived thymic stromal lymphopoietin (TSLP), to produce IL-12p70, and to favor the generation of Th1 cells. DCs activated via dectin-1, but not those activated with TLR-7/8 ligand or poly I:C, induce CD8+ T cells to express CD103 (αE integrin), a ligand for cancer cells, E-cadherin. Generation of these mucosal CD8+ T cells is regulated by DC-derived integrin αvβ8 and TGF-β activation in a dectin-1-dependent fashion. These CD103+ CD8+ mucosal T cells accumulate in the tumors, thereby increasing cancer necrosis and inhibiting cancer progression in vivo in a humanized mouse model of breast cancer. Importantly, CD103+ CD8+ mucosal T cells elicited by reprogrammed DCs can reject established cancer. Thus, reprogramming tumor-infiltrating DCs represents a new strategy for cancer rejection.

Topics: Animals; beta-Glucans; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Dendritic Cells; Disease Models, Animal; Female; Humans; Lectins, C-Type; Mice; Mucous Membrane; Signal Transduction; T-Lymphocyte Subsets; Th2 Cells; Transforming Growth Factor beta

An aminated beta-1,3-D-glucan derivative of curdlan is reported to render macrophages cytostatic to L-929 cells and to potentiate macrophage cytotoxicity to the tumor cells in vitro.

Topics: Animals; Ascitic Fluid; beta-Glucans; Cell Line; Cell Transformation, Neoplastic; Cells, Cultured; Cytotoxicity, Immunologic; Dose-Response Relationship, Drug; Fibroblasts; Glucans; Macrophages; Mice; Mice, Inbred C3H; Mice, Inbred DBA