Interleukin (IL)-23, composed of p19 and p40 subunits, has diverse functions in regulating immune systems, enhancing cell-mediated immunity. In the present study, we investigated whether forced expression of the p19-linked p40 gene in murine
mammary cancer cells (MA891) produced antitumor effects in vivo.
Tumor growth of MA-891 cells expressing
IL-23 (IL-23/MA891) in mice was retarded compared with parental and vector
DNA-transduced
tumors and survival of the mice inoculated with IL-23/MA-891 cells was prolonged. Expressions of the CD4(+) T cells and CD8(+) T cells were up-regulated not only in IL-23/MA-891
tumor specimens but also in spleen cells of mice inoculated with IL-23/MA-891 as compared with those of mice inoculated with parental or vector
DNA-transduced
tumors. Cytotoxic CD8(+) T lymphocyte (CTL) activity of spleen cells from mice inoculated with IL-23/MA-891 was also significantly higher than the other two groups. Th1-type
cytokines such as
interferon-gamma,
TNF-alpha and IL-12p70 secreted from spleen cells of mice bearing IL-23/MA-891
tumors were increased while Th2-type
cytokine IL-4 was negative regulated. Moreover, we have identified that the quantity of DC in spleen cells of mice bearing IL-23/MA-891
tumors was increased as compared with those mice bearing parental or vector
DNA-transfected
tumors.