OK‐432 synergizes with IFN‐γ to confer dendritic cells with enhanced antitumor immunity

Generation of functional dendritic cells (DCs) with boosted immunity after the withdrawal of initial activation/maturation conditions remains a significant challenge. In this study, we investigated the impact of a newly developed maturation cocktail consisting of OK‐432 and interferon‐gamma (IFN‐γ) on the function of human monocyte‐derived DCs (MoDCs). We found that OK‐432 plus IFN‐γ stimulation could induce significantly stronger expression of surface molecules, production of cytokines, as well as migration of DCs compared with OK‐432 stimulation alone. Most importantly, DCs matured with OK‐432 plus IFN‐γ‐induced maintained secretion of interleukin‐12 (IL‐12)p70 in secondary culture after stimulus withdrawal. Functionally, OK‐432 plus IFN‐γ‐conditioned DCs induce remarkable Th1 and Tc1 responses more effectively than OK‐432 alone, even more than the use of α‐type‐1 cytokine cocktail. As a result, DCs matured with OK‐432 plus IFN‐γ can prime stronger cytotoxic lymphocyte (CTL) and natural killer (NK) cell response against tumor cells in vitro . Peripheral blood mononuclear cells activated by DCs matured with OK‐432 plus IFN‐γ also showed greater tumor growth inhibition in vivo in null mice. Molecular mechanistic analysis showed that DC maturation using IFN‐γ in concert with OK‐432 involves the activation of p38 and nuclear factor‐kappa B (NF‐κB) pathways. This study provided a novel strategy to generate more potent immune segments in DC vaccine.