[The anti-tumor efforts of thymosin alpha1 on tumor lysate-pulsed dendritic cells in colon cancer in vitro and in vivo]
ABSTRACT
AIM: To investigate the effects of thymosin alpha1 (Talpha1) on the differentiation, maturation and function of tumor lysate-pulsed dendritic cells (LyDCs) in vitro, and to study the antitumor effects on tumor models of the nude mice bearing colon cancer in vivo.
METHODS: Immature DCs (imDCs) were prepared routinely from human peripheral blood mononuclear cells. The LyDCs were prepared from the imDCs loaded with lysate of HT-29 tumor cell line. The phenotypes of imDCs and LyDCs pre- or post-stimulated by Talpha1 were analyzed by flow cytometry. Autologous T cells were cocultured with LyDCs in the presence or absence of Talpha1 2 days later. IL-12 secretion of LyDCs and IFN-gamma secretion of the activated T cells in the supernatants were measured by ELISA. The in vitro cytotoxicity of antigen specific cytotoxic T lymphocytes (CTLs) induced by LyDCs which were treated with Talpha1 was evaluated by MTT assay. A humanized nude mice model bearing colon cancer was established. The in vivo antitumor activity was evaluated in the humanized nude mice after the treatment with LyDCs plus Talpha1 or LyDCs alone.
RESULTS: The expression levels of HLA-DR, CD80, CD86 and CD83 in imDCs and LyDCs were markedly up-regulated after the stimulation with Talpha1 respectively (P<0.01). The levels of IL-12 and IFN-gamma were also significantly increased in the presence of Talpha1 (P<0.05 and P<0.01, respectively). Cytotoxicity induced by LyDCs treated with Talpha1 was significantly enhanced (P<0.01) as compared with LyDCs in vitro. The humanized cellular immunity was successfully established in the nude mice model. On the 58 th day after the inoculation of tumor cells, the inhibitory rate of tumor growth was significantly higher in the group treated with LyDCs plus Talpha1 than that in the group treated with LyDCs alone (60.41% and 37.20%, respectively; P<0.01).
CONCLUSION: Talpha1 can induce the functional maturation of DCs and enhance the immune response of CD4+Th1 arm and cytotoxicity induced by LyDCs. Talpha1 has a synergistic antitumor effect. It might be a promising adjuvant candidate for DC-based immunotherapy of gastrointestinal carcinomas.