Immunosuppressive effect of bladder cancer on function of dendritic cells involving of Jak2/STAT3 pathway

Abstract

Function of dendritic cells (DCs) is impaired by some cancer cells. However, the effect of bladder cancer cell (BCC) on phenotype and function of DCs remains unclear. In this study, healthy human peripheral blood mononuclear cells (PBMCs) derived DCs were co-cultured with BCC pumc-91 and adriamycin-resistant pumc-91/ADM. The expression of DC markers and costimulatory molecules decreased after co-culture. Co-cultured DCs rapidly underwent apoptosis, and had a declined capability to produce IL-8 and RANTES. Furthermore, co-cultured DCs showed impaired allogeneic T cell proliferation and T cell-derived cytokine secretion. Finally, AG490, a Jak2/STAT3 inhibitor, restored the expression of DC markers and costimulatory molecules. Of note, compared with control DCs, DCs co-cultured with pumc-91 produced more IP-10; DCs co-cultured with pumc-91/ADM secreted more MIG. Taken together, these results suggest BCC may inhibit maturation and function of DCs involving of Jak2/STAT3 pathway, and there may be different mechanisms by which adriamycin-resistant BCC restrains DC function in antitumor immune response.