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Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity¹

Zuqiang Liu^*, Jin H. Kim^*, Louis D. Falo, Jr.^*, and Zhaoyang You^2,*,,

^* Department of Dermatology and Department of Immunology, University of Pittsburgh School of Medicine and The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213

Regulatory T cell (Treg) from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4⁺ T cell activity is comparable to Treg from naive mice (naive Treg), only tumor Treg suppress naive CD8⁺ T cell activation and DC function. Neither tumor Treg nor naive Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively transferred tumor-primed CD4⁺ T cells. This is consistent with the observation that, in this model, neither tumor Treg nor naive Treg can inhibit effectors in vitro or in vivo. However, tumor Treg abrogate tumor-specific CD8⁺ T cell responses in tumor-draining lymph nodes and antitumor immunity at the early stage of the immune response induced by adoptively transferred tumor-primed CD4⁺ T cells. These data indicate that, in this model, tumor Treg potently abrogate tumor-specific CD8⁺ T cell responses in tumor-draining lymph nodes, thereby suppressing antitumor immunity at the early stage of the immune response induced by adoptively transferred tumor-primed CD4⁺ T cells.

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 a start-up fund from Department of Dermatology of The University of Pittsburgh, and by National Institutes of Health Grant R01CA108813 (to Z.Y.), P01CA73743, R01AI060008, and R01CA106662 (to L.D.F.).

² Address correspondence and reprint requests to Dr. Zhaoyang You, W1046 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213. E-mail address: youz{at}upmc.edu

³ Abbreviations used in this paper: Treg, CD4⁺CD25⁺ regulatory T cell; DC, dendritic cell; TDLN, tumor-draining lymph node.