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.
Shah
A H
AH
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611-3009, USA.
Lee
C
C
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000502:physiology
D016212:Transforming Growth Factor beta