TGF-beta-independent induction of immunogenicity by decorin gene transfer in human malignant glioma cells

Ectopic expression of the proteoglycan, decorin, abrogates the growth of ex perimental C6 gliomas in the rat. Since gliomas release large amounts of tr ansforming growth factor-beta (TGF-beta) and since decorin is a TGF-beta an tagonist, decorin gene transfer-mediated abrogation of glioma growth in viv o may involve enhanced immunogenicity of the tumor cells. Here, we report t hat human glioma cells stimulate alloreactive immune responses when enginee red to express decorin whereas parental glioma cells are non-immunogenic in vitro. The alloreactive immune response is mediated by CD8(+) and CD4(+) T cells as well as by NK cells. The immunosuppression exerted by parental or mock-transfected glioma cells is mediated by soluble factors and can in pa rt be mimicked by exogenous TGF-beta. However, neutralizing anti-TGF-beta a ntibodies do not reverse glioma-mediated immunosuppression, suggesting that decorin abrogates glioma-induced immune cell inhibition by interfering wit h the activity of other, so far unidentified glioma-secreted mediators. We conclude that enhanced immunogenicity may mediate the antineoplastic effect s of decorin gene therapy for malignant glioma but that factors other than TGF-beta may be responsible for glioma-induced immunosuppression.