Cytidine-phosphate-guanosine oligodeoxynucleotides and interferon-alpha-expressing tumor cells effectively induce dendritic cell maturation in vitro.

Background: Dendritic cells (DCs) play an important role in immune response and cytidine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODN) as well as interferon (IFN)-alpha have been proven to induce DC maturation. In this study, the synergistic effects of CpG-ODN and IFN-alpha on DC maturation were evaluated. Materials and Methods: Surface molecules on DCs and the stimulatory responses of DCs to allogeneic splenocytes were analyzed after cultivation with CpG-ODN and IFN-alpha-overexpressing murine colorectal cancer MC38 cells (MC38-IFN alpha). Results: Co-incubation with CpG-ODN and MC38-IFNa, but not wild-type MC38 cells (MC38-WT), effectively up-regulated co-stimulatory molecules on the DCs. CpG, in combination with IFN-a, stimulated IL-1 beta and TNF-alpha production by DCs eftective. When DCs preincubated with CpG-ODN and MC38-IFNa were co-incubated with allogeneic splenocytes in vitro, the proliferation of these splenocytes was significantly enhanced compared with that of splenocytes incubated with CpG-ODN and MC38-WT cells (p = 0.041). Conclusion: Since CpG-ODN and IFN-a have synergistic effects on DC maturation, they may induce potent antitumor immune responses and combination therapy should be considered for clinical application.