Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy

Cancers have developed numerous mechanisms for escaping the immune response, either by successfully evading a fully functional immune system or by actively suppressing the immune system so that they are no longer recognised or effectively eliminated. Current evidence supports active cancer cell-mediated immunosuppression via the secretion of the potent immunosuppressive cytokine, transforming growth factor-beta (TGF-beta), as the most general and potent mechanism for human cancer cells to escape the immune system. Efforts to bypass TGF-beta-mediated immunosuppression thereby represent an attractive therapeutic strategy for the chemoprevention and treatment of human cancers, both by directly increasing the efficacy of immunosurveillance and by increasing the efficacy of current immunotherapy strategies. Current approaches are limited by their nonspecific effects on the TGF-beta signalling pathway, as TGF-beta pathways which specifically mediate immunosuppression have not yet been defined. Future efforts should be directed towards elucidating specific TGF-beta pathways so that these can be targeted for the chemoprevention and treatment of human cancers.