Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells.
Despite the existence of tumor-specific antigens and demonstrated presence of tumor-specific immune cells, the majority of tumors manage to avoid immune-mediated destruction. Various mechanisms have been suggested for tumor evasion from immune response. One such mechanism is thought to be mediated by transforming growth factor-beta (TGF-beta), an immunosuppressive cytokine found at the site of most tumors. We demonstrate here that T-cell-specific blockade of TGF-beta signaling allows the generation of an immune response capable of eradicating tumors in mice challenged with live tumor cells. In addition, we provide mechanisms through which abrogation of TGF-beta signaling leads to the enhancement of anti-tumor immunity. Our data indicate that T-cell-specific blockade of TGF-beta signaling has strong therapeutic potential to shift the balance of the immune response in favor of anti-tumor immunity.
Gorelik
L
L
Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, Connecticut, USA.
Flavell
R A
RA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II