Bryostatin-1 enhances the maturation and antigen-presenting ability of murine and human dendritic cells
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- Bryostatin-1 enhances the maturation and antigen-presenting ability of murine and human dendritic cells
- Do, Yoonkyung; Hegde, VL; Nagarkatti, PS; Nagarkatti, M
- PROTEIN-KINASE-C; COLONY-STIMULATING-FACTOR; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; PHASE-I; SYNGENEIC TUMOR; DOWN-REGULATION; LEUKEMIA-CELLS; LYMPHOCYTES-T; TNF-ALPHA
- Issue Date
- AMER ASSOC CANCER RESEARCH
- CANCER RESEARCH, v.64, no.18, pp.6756 - 6765
- In this study, we investigated the effect of bryostatin-1 (Bryo-1), an antineoplastic agent, on dendritic cell (DC) maturation, activation, and functions. Murine bone marrow-derived DCs on culture with Bryo-1 alone, Bryo-1 + calcium ionophore (CI), but not CI alone exhibited morphologic changes characteristic of mature DCs and expressed increased levels of CD40, CD80, and CD86. Moreover, Bryo-1 + CI-treated DCs exhibited enhanced antigen-presenting ability to naive and antigen-specific T cells and alloreactive T cells. Bryo-1 + CI-mediated activation of DCs involved protein kinase C (PKC), especially PKC-α, δ, and - ι, and addition of PKC inhibitors impaired their ability to activate T cells. Bryo-1 + CI treatment of DCs did not activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase, p38 MAPK, or stress-activated protein kinase/c-Jun NH 2-terminal kinase pathways. Finally, treatment of DCs with Bryo-1 alone and Bryo-1 + CI, but not CI alone, induced nuclear translocation of nuclear factor κB as studied by confocal microscopy. DCs generated from human peripheral blood monocytes or from human cord blood CD34 + hematopoietic stem cells, when cultured with Bryo-1 + CI, also showed maturation and increased T-cell stimulatory activity. Bryo-1 + CI was more potent in inducing maturation and activation of DCs when compared with other agents such as tumor necrosis factor α, lipopolysaccharide, or phorbol 12-myristate 13-acetate + CI. Collectively, the current study shows for the first time that Bryo-1 alone or in combination with CI may promote the maturation of DCs and therefore may be useful in development of DC-based cancer immunotherapy.
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