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.


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-IFNalpha).


RESULTS
Co-incubation with CpG-ODN and MC38-IFNalpha, but not wild-type MC38 cells (MC38-WT), effectively up-regulated co-stimulatory molecules on the DCs. CpG, in combination with IFN-alpha, stimulated IL-1beta and TNF-alpha production by DCs effectively. When DCs preincubated with CpG-ODN and MC38-IFNalpha 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).


CONCLUSIONS
Since CpG-ODN and IFN-alpha have synergistic effects on DC maturation, they may induce potent antitumor immune responses and combination therapy should be considered for clinical application.
Hiraide
Ayako
A
Second Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
Hiroishi
Kazumasa
K
Ishii
Shigeaki
S
Eguchi
Junichi
J
Imawari
Michio
M
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000276:immunology; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016898:Interferon-alpha; D009841:Oligonucleotides