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Cutting Edge: Th17 and Regulatory T Cell Dynamics and the Regulation by IL-2 in the Tumor Microenvironment¹

Ilona Kryczek^*, Shuang Wei^*, Linhua Zou^*, Saleh Altuwaijri^*, Wojciech Szeliga^*, Jay Kolls, Alfred Chang^* and Weiping Zou^2,*

^* Department of Surgery, University of Michigan, Ann Arbor, MI 48109; and Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213

Th17 cells play an active role in inflammation and autoimmune diseases. However, the nature and regulation of Th17 in the context of tumor immunity remain unknown. In this study, we show that parallel to regulatory T (Treg) cells, IL-17⁺ CD4⁺ and CD8⁺ T cells are kinetically induced in multiple tumor microenvironments in mice and humans. Treg cells play a crucial role in tumor immune pathogenesis and temper immune therapeutic efficacy. IL-2 is crucial for the production and function of Treg cells. We now show that IL-2 reduces IL-17⁺ T cell differentiation in the tumor microenvironment accompanied with an enhanced Treg cell compartment in vitro and in vivo. Altogether, our work demonstrates a dynamic differentiation of IL-17⁺ T cells in the tumor microenvironment, reveals a novel role for IL-2 in controlling the balance between IL-17⁺ and Treg cells, and provides new insight of IL-17⁺ T cells in tumor immune pathology and therapy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the National Cancer Institute (W.Z.).

² Address correspondence and reprint requests to Dr. Weiping Zou, University of Michigan School of Medicine, C560B MSRB II, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0669. E-mail: wzou{at}umich.edu

³ Abbreviations used in this paper: Treg, regulatory T; MCA, 3-methylcholanthrene.

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