Endogenous interleukin-l8 modulates immune escape of murine melanoma cells

다국어 초록 (Multilingual Abstract)

It has been known that melanoma cells can suppress the immune system by the Fas ligand. The present study investigated whether interleukin(IL)-18, which can enhance Fas ligand expression, is produced by B16F10 melanoma cells and is involved in immune escape of tumor cells. Immunohistology, RT-PCR, intracellular FACS analysis, and immunoblotting demonstrated that melanoma cells express IL-18. In addition to IL-18, the IL-18 receptor was also detected in B16F10 melanoma cells, suggesting a role of this cytokine in regulating the functions of B16F10 melanoma cells. The functional effect of IL-18 on B16F10 melanoma cells was shown by reduction of Fas ligand expression in cells transfected with IL-18 antisense cDNA. In addition, the same treatments decreased intracellular reactive oxygen intermediate levels in B16F10 melanoma cells, indicating that IL-18 regulates reactive oxygen intermediate production. Furthermore, transfection of IL-18 antisense cDNA into melanoma cells increased the susceptibility of tumor cells to natural killer cells in vitro. When IL-18 antisense transfectants were implanted into syngeneic mice, severe reduction of tumor cell growth was observed. Taken together, these results demonstrate that IL-18 has a critical role as a survival factor for B16F10 melanoma cells.