Hiraide Ayako, Hiroishi Kazumasa, Ishii Shigeaki, Eguchi Junichi, Imawari Michio
Second Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
Anticancer Res. 2006 Jan-Feb;26(1A):211-8.
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.
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).
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).
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.
树突状细胞（DCs）在免疫反应中发挥重要作用，且已证实胞嘧啶-磷酸-鸟嘌呤（CpG）寡脱氧核苷酸（ODN）以及干扰素（IFN）-α可诱导DC成熟。在本研究中，评估了CpG-ODN与IFN-α对DC成熟的协同作用。
在用CpG-ODN和过表达IFN-α的小鼠结直肠癌MC38细胞（MC38-IFNα）培养后，分析DC表面分子以及DC对同种异体脾细胞的刺激反应。
与CpG-ODN和MC38-IFNα共同孵育，而非野生型MC38细胞（MC38-WT），可有效上调DC上的共刺激分子。CpG与IFN-α联合可有效刺激DC产生IL-1β和TNF-α。当预先用CpG-ODN和MC38-IFNα孵育的DC与同种异体脾细胞在体外共同孵育时，与用CpG-ODN和MC38-WT细胞孵育的脾细胞相比，这些脾细胞的增殖显著增强（p = 0.041）。
由于CpG-ODN和IFN-α对DC成熟具有协同作用，它们可能诱导强大的抗肿瘤免疫反应，临床应用中应考虑联合治疗。
