T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis

Cancer Res. 2009 Jul 1;69(13):5490-7. doi: 10.1158/0008-5472.CAN-09-0304.


T-regulatory (Treg) cells play a major role in cancer by suppressing protective antitumor immune responses. A series of observations (from a single laboratory) suggest that Treg cells are protective in cancer by virtue of their ability to control cancer-associated inflammation in an interleukin (IL)-10-dependent manner. Here, we report that the ability of Treg cells to produce IL-10 and control inflammation is lost in the course of progressive disease in a mouse model of hereditary colon cancer. Treg cells that expand in adenomatous polyps no longer produce IL-10 and instead switch to production of IL-17. Aberrant Treg cells from polyp-ridden mice promote rather than suppress focal mastocytosis, a critical tumor-promoting inflammatory response. The cells, however, maintain other Treg characteristics, including their inability to produce IL-2 and ability to suppress proliferation of stimulated CD4 T cells. By promoting inflammation and suppressing T-helper functions, these cells act as a double-edged knife propagating tumor growth.

Publication types

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

MeSH terms

  • Adenomatous Polyposis Coli / complications*
  • Adenomatous Polyposis Coli / immunology*
  • Adoptive Transfer
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Inflammation / immunology*
  • Interleukin-10 / physiology
  • Interleukin-17 / biosynthesis
  • Lymphocyte Activation
  • Mast Cells / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Phenotype
  • Stem Cells / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Interleukin-17
  • Interleukin-10