T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer

Oncotarget. 2011 Dec;2(12):1339-51. doi: 10.18632/oncotarget.403.

Abstract

During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development. Here, using a transgenic model of mammary cancer, we report that deletion of TGF-β1 from tumor cells did not protect mice from tumor development. However, ablation of TGF-β1 from T cells significantly inhibited mammary tumor growth. Additionally, absence of TGF-β1 in T cells prevented tumors from advancing to higher pathological grades and further suppressed secondary tumor development in the lungs. These findings reveal T cells but not tumor cells as a critical source of TGF-β1 that promotes tumor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Mammary Neoplasms, Animal / metabolism
  • Mammary Neoplasms, Animal / pathology*
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes / metabolism*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Transforming Growth Factor beta