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

Abstract

The effect of treatment with interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), vincristine, and etoposide was evaluated on the secretion of transforming growth factor-beta (TGF-beta) 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-1 beta, IFN-gamma, and/or anticancer agents (vincristine and etoposide). Combined treatment with IL-1 beta and IFN-gamma caused greater inhibition of TGF-beta secretion compared to treatment with IFN-gamma, and almost the same levels of inhibition as treatment with vincristine and etoposide. The greatest inhibition of TGF-beta 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-1 beta, IFN-gamma, 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-beta and IL-10 secretion by malignant glioma cells can be suppressed by treatment with a combination of IL-1 beta, IFN-gamma, 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.