Münz C, Naumann U, Grimmel C, Rammensee H G, Weller M
Department of Immunology, Institute for Cell Biology, University of Tübingen Medical School, Germany.
Eur J Immunol. 1999 Mar;29(3):1032-40. doi: 10.1002/(SICI)1521-4141(199903)29:03<1032::AID-IMMU1032>3.0.CO;2-W.
Ectopic expression of the proteoglycan, decorin, abrogates the growth of experimental C6 gliomas in the rat. Since gliomas release large amounts of transforming growth factor-beta (TGF-beta) and since decorin is a TGF-beta antagonist, decorin gene transfer-mediated abrogation of glioma growth in vivo may involve enhanced immunogenicity of the tumor cells. Here, we report that human glioma cells stimulate alloreactive immune responses when engineered 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 part be mimicked by exogenous TGF-beta. However, neutralizing anti-TGF-beta antibodies do not reverse glioma-mediated immunosuppression, suggesting that decorin abrogates glioma-induced immune cell inhibition by interfering with the activity of other, so far unidentified glioma-secreted mediators. We conclude that enhanced immunogenicity may mediate the antineoplastic effects of decorin gene therapy for malignant glioma but that factors other than TGF-beta may be responsible for glioma-induced immunosuppression.
蛋白聚糖核心蛋白聚糖的异位表达可消除大鼠实验性C6胶质瘤的生长。由于胶质瘤会释放大量转化生长因子-β（TGF-β），且核心蛋白聚糖是一种TGF-β拮抗剂，因此核心蛋白聚糖基因转移介导的体内胶质瘤生长消除可能涉及肿瘤细胞免疫原性的增强。在此，我们报告，经基因工程改造表达核心蛋白聚糖的人胶质瘤细胞可刺激同种异体反应性免疫应答，而亲本胶质瘤细胞在体外无免疫原性。同种异体反应性免疫应答由CD8 +和CD4 + T细胞以及NK细胞介导。亲本或 mock转染的胶质瘤细胞施加的免疫抑制由可溶性因子介导，并且部分可由外源性TGF-β模拟。然而，中和抗TGF-β抗体并不能逆转胶质瘤介导的免疫抑制，这表明核心蛋白聚糖通过干扰其他尚未确定的胶质瘤分泌介质的活性来消除胶质瘤诱导的免疫细胞抑制。我们得出结论，免疫原性增强可能介导核心蛋白聚糖基因治疗恶性胶质瘤的抗肿瘤作用，但TGF-β以外的因素可能是胶质瘤诱导免疫抑制的原因。
