Immunosuppression in tumor microenvironments is one of the critical issues for cancer immunotherapy. We have been demonstrated that IL-6, a pleiotropic cytokine that regulate the growth, differentiation and survival of a variety of cells, significantly inhibited maturation of murine dendritic cells (DCs) via STAT3 activation both in vitro and in vivo. In this study, we focused on IL-6/STAT3-signaling cascade in human dendritic cells (DCs), and investigated the effects of IL-6 on antigen-presenting ability of DCs. Surface HLA class I, HLA class II, and costimulatory molecules of human DCs were evaluated after the stimulation with IL-6 in vitro. As a result, HLA-DR and CD86 expressions were significantly reduced by IL-6 treatment of human DCs. The reduction was remarkably blocked in the presence of STAT3 inhibitor. In addition, IFN-γ production by T cells after TCR-stimulation was significantly suppressed in the presence of IL-6-treated DCs compared with control DCs. Moreover, we found that activation of antigen-specific CD4+ T cells by DCs was remarkably reduced by the IL-6-treatment. In this study, we demonstrated that IL-6/STAT3-signaling cascade was one of the regulating factors for antigen presentation of DCs. From these findings suggest that IL-6/STAT3 signaling cascade regulates immunosuppressive function of human DCs, which would be a promising target for improving the effects of cancer immunotherapy.

2014