T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-β1 cytokine

Immunity. 2011 Jul 22;35(1):123-34. doi: 10.1016/j.immuni.2011.04.019. Epub 2011 Jul 14.

Abstract

Tolerance induction in T cells takes place in most tumors and is thought to account for tumor evasion from immune eradication. Production of the cytokine TGF-β is implicated in immunosuppression, but the cellular mechanism by which TGF-β induces T cell dysfunction remains unclear. With a transgenic model of prostate cancer, we showed that tumor development was not suppressed by the adaptive immune system, which was associated with heightened TGF-β signaling in T cells from the tumor-draining lymph nodes. Blockade of TGF-β signaling in T cells enhanced tumor antigen-specific T cell responses and inhibited tumor development. Surprisingly, T cell- but not Treg cell-specific ablation of TGF-β1 was sufficient to augment T cell cytotoxic activity and blocked tumor growth and metastases. These findings reveal that T cell production of TGF-β1 is an essential requirement for tumors to evade immunosurveillance independent of TGF-β produced by tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Growth Processes / genetics
  • Cell Growth Processes / immunology
  • Cytotoxicity, Immunologic / genetics
  • Cytotoxicity, Immunologic / immunology
  • Disease Models, Animal
  • Humans
  • Immune Tolerance
  • Immunologic Surveillance
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Transgenic
  • Oncogenes / physiology
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Receptors, Antigen, T-Cell / genetics
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*
  • Tumor Escape

Substances

  • Receptors, Antigen, T-Cell
  • Transforming Growth Factor beta