The dual adverse effects of TGF-beta secretion on tumor progression.
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.
Trapani
Joseph A
JA
Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, 3002, Australia. joe.trapani@petermac.org
D051696:Activating Transcription Factors / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D053804:Granzymes; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013945:Thymoma / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*; D019139:Tumor Escape
D051696:Activating Transcription Factors; D000970:Antineoplastic Agents; D001798:Blood Proteins; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016212:Transforming Growth Factor beta; D054353:Perforin; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases