Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells

Nat Med. 2001 Oct;7(10):1118-22. doi: 10.1038/nm1001-1118.

Abstract

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.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II