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

Elias Gounaris, Nichole R. Blatner, Kristen Dennis, Fay Magnusson, Michael F. Gurish, Terry B. Strom, Philipp Beckhove, Fotini Gounari, Khashayarsha Khazaie

Research output: Contribution to journalArticlepeer-review

133 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5490-5497
Number of pages8
JournalCancer research
Volume69
Issue number13
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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