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.
Second Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
Ayako
A
Hiraide
Kazumasa
K
Hiroishi
Shigeaki
S
Ishii
Junichi
J
Eguchi
Michio
M
Imawari
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