TGF-beta-based immunotherapy for cancer: breaching the tumor firewall

Many malignant cells secrete transforming growth factor-beta (TGF-beta), a potent immunosuppresant, suggesting that TGF-beta production may represent a significant tumor escape mechanism from host immunosurveillance. Establishment of a leukocyte subpopulation with disrupted TGF-beta signaling in the tumor-bearing host offers a potential means for immunotherapy of cancer. Downregulation of TGF-beta secretion in tumor cells results in restoration of immunogenicity in the host, while T-cell insensitivity to TGF-beta results in accelerated differentiation and autoimmunity, elements of which may be required in order to combat self-antigen-expressing tumors in a tolerized host. The rationale, approaches, and potential pitfalls of this strategy will be discussed.