Trapani Joseph A
Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, 3002, Australia.
Cancer Cell. 2005 Nov;8(5):349-50. doi: 10.1016/j.ccr.2005.10.018.
When a cancer escapes the growth-inhibitory effects of TGF-beta secreted by cancer cells themselves or by cells in the local stroma, a further adverse outcome for the host is the associated TGF-beta-induced suppression of anticancer T cell immunity. In addition to the previously described dampening of T cell activation and proliferation, TGF-beta markedly and directly suppresses the transcription of genes encoding multiple key proteins of the "cytotoxic program" of CD8+ CTL, such as perforin and granzymes, cytotoxins that act through the granule exocytosis pathway. The findings described below suggest that TGF-beta and its signaling pathways will be major targets for novel cancer therapeutics.
当癌症逃脱癌细胞自身或局部基质细胞分泌的转化生长因子β（TGF-β）的生长抑制作用时，宿主面临的另一个不良后果是TGF-β诱导的抗癌T细胞免疫抑制。除了之前描述的T细胞活化和增殖受抑制外，TGF-β还显著且直接地抑制编码CD8+细胞毒性T淋巴细胞（CTL）“细胞毒性程序”多种关键蛋白的基因转录，如穿孔素和颗粒酶，这些细胞毒素通过颗粒胞吐途径发挥作用。以下所述的研究结果表明，TGF-β及其信号通路将成为新型癌症治疗的主要靶点。
