T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis.
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.
Gounaris
Elias
E
Division of Gastroenterology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3015, USA.
Blatner
Nichole R
NR
Dennis
Kristen
K
Magnusson
Fay
F
Gurish
Michael F
MF
Strom
Terry B
TB
Beckhove
Philipp
P
Gounari
Fotini
F
Khazaie
Khashayarsha
K
D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D020381:Interleukin-17; D016753:Interleukin-10