Down-regulation of transforming growth factor-β and interleukin-10 secretion from malignant glioma cells by cytokines and anticancer drugs

The effect of treatment with interleukin-1β (IL-1β), interferon-γ (IFN-γ), vincristine, and etoposide was evaluated on the secretion of transforming growth factor-β (TGF-β) and IL-10 and the expression of major histocompatibility complex (MHC) class I, intercellular adhesion molecule-1 (ICAM-1), and CD80 molecules by malignant glioma cells. Five malignant glioma cell lines were treated with IL-1β, IFN-γ, and/or anticancer agents (vincristine and etoposide). Combined treatment with IL-1β and IFN-γ caused greater inhibition of TGF-β secretion compared to treatment with IFN-γ, and almost the same levels of inhibition as treatment with vincristine and etoposide. The greatest inhibition of TGF-β secretion was achieved by treatment with all agents. Low levels of IL-10 secretion were determined in two out of five malignant glioma cell lines. This IL-10 secretion was inhibited by treatment with IL-1β, IFN-γ, vincristine, and/or etoposide. Treatment with both cytokines and anticancer agents increased the expression of MHC class I and ICAM-1 in all tumor cell lines. The mean increase of expression of MHC class I was 50% and that of ICAM-1 was 12-fold. No tumor cell lines expressed CD80 molecules on the cell surface, and no treatment caused CD80 expression. These results suggest that TGF-β and IL-10 secretion by malignant glioma cells can be suppressed by treatment with a combination of IL-1β, IFN-γ, vincristine, and etoposide, and the treatment up-regulates MHC class I and ICAM-1 expression on tumor cells. These results have implications for immunotherapy and chemotherapy in patients with malignant tumors.