The dual adverse effects of TGF-β secretion on tumor progression

Summary

When a cancer escapes the growth-inhibitory effects of TGF-β secreted by cancer cells themselves or by cells in the local stroma, a further adverse outcome for the host is the associated TGF-β-induced suppression of anticancer T cell immunity. In addition to the previously described dampening of T cell activation and proliferation, TGF-β 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-β and its signaling pathways will be major targets for novel cancer therapeutics.