Immunostimulatory and anti-neoplasm effects of anovel palindrome CpG oligodeoxynucleotide in mice

Aim： DNAs containing unmethylated CpG motifs can stimulate innate and adaptive immunity. The aim of this study was to investigate the immunostimulatory and anti-neoplasm effects of a novel CpG oligodeoxynucleotide, ODNIO, in tumor-bearing mice. Methods： B16 melanoma-bearing C57BL/6 mice were administered ip or sc with ODNIO or conventional CpG 0DN1826 on the indi- cated days post inoculation. The animal survival rate and the inhibitory effect on tumor growth were observed in vivo. B and T lym-phocyte proliferation, natural killing cell cytotoxicity and the phagocytic ability of peritoneal macrophages from the animals were deter- mined using [3H]-thymidine incorporation assay, 4-h^51Cr release assay and neutral red chromometry method, respectively. The serum levels of IL-12, IL-4, and IgE were quantified using ELISA assays. Histological examination of tumor tissues was performed after HE staining, and the expression of PCNA, CD63, and CD80 in tumor tissues was analyzed with immunohistochemistry. Results： ODNIO （1, 5, and 25 mg/kg） significantly inhibited the growth and metastasis of the tumor, and significantly prolonged the survival of tumor-bearing mice, as compared with 0DN1826. The immune status was suppressed in tumor-bearing mice. Both ODNIO and 0DN1826 significantly reversed the suppressed immunoactivities in tumor-bearing mice, which included promoting B and T lym-phocyte proliferation, enhancing NK cell and peritoneal macrophage activities, inducing IL-12 secretion and inhibiting 11-4 and IgE secretion. Further, CpG ODNs decreased PCNA and CD63 expression while induced expression of CD80. ODNIO presented more potent activity, and displayed the most prominent immunostimulatory potential. Conclusion： ODNIO produces prominent immunomodutatory effects on cellular immunity in tumor-bearing mice, which might help reverse the established Th2-type responses to the Thl-type responses, thus may be used as a potent anti-tumor immunotherapy agent or adjuvant.