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T-Regulatory Cells Shift from a Protective Anti-Inflammatory to a Cancer-Promoting Proinflammatory Phenotype in Polyposis

¹ Division of Gastroenterology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine; ² Committee on Immunology, Department of Medicine, The University of Chicago, Chicago, Illinois; ³ Department of Immunology, Center for Cancer Immunology, M. D. Anderson Cancer Center, University of Texas, Houston, Texas; ⁴ Division of Rheumatology, Immunology, and Allergy, Departments of Medicine and Pathology, Brigham and Women's Hospital and Harvard Medical School; ⁵ The Transplant Research Center, Division of Immunology, Harvard Medical School, Boston, Massachusetts; and ⁶ Translational Immunology Unit, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Requests for reprints: Khashayarsha Khazaie, Division of Gastroenterology and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, 303 East Superior Street, 3-111 Lurie, Chicago, IL 60611-3015. Phone: 312-503-1901; Fax: 312-503-0386; E-mail: khazaie{at}northwestern.edu.

Key Words: mast cells • polyposis • T-regulatory cells

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. [Cancer Res 2009;69(13):5490–7]

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