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Cutting Edge: Tumor-Specific CD8⁺ T Cells Infiltrating Prostatic Tumors Are Induced to Become Suppressor Cells¹

Kimberly A. Shafer-Weaver,^* Michael J. Anderson,^* Katherine Stagliano,^* Anatoli Malyguine, Norman M. Greenberg, and Arthur A. Hurwitz^2*

^*Tumor Immunity and Tolerance Section, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute-Frederick, Frederick, MD 21702; Laboratory of Cell-Mediated Immunity, SAIC-Frederick, Inc., Frederick, MD 21702; and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

We previously reported that naive, tumor-specific CD8⁺ (TcR-I) T cells transferred into prostate tumor-bearing mice traffic to the prostate where they become tolerized. We now report that TcR-I cells suppress the proliferation of naive T cells. This suppression is mediated at least in part by secreted factors, and the suppressive activity can be blocked by Abs directed against TGF-β. We further report that TcR-I cells must infiltrate the prostate to acquire suppressive activity. Delivery of tumor-specific CD4⁺ T cells prevents the conversion of TcR-I cells into suppressor cells. Taken together, our findings may have critical implications for sustaining T cell responsiveness during immunotherapy, as the development of suppressor cells in the tumor microenvironment may eliminate the potency of T cells primed in the periphery or delivered during adoptive immunotherapy.

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 Intramural Research Program of the National Cancer Institute, National Institutes of Health and the Department of Defense Prostate Cancer Research Program and has been funded in part with federal funds under contract N01-CO-12400 (to K.A.S.-W. and A.M.). K.A.S.-W. was a predoctoral student in the Immunology Program of the Institute for Biomedical Sciences at George Washington University, Washington DC, and this work is from a dissertation in partial fulfillment of the requirements for the Ph.D. degree.

² Address correspondence and reprint requests to Dr. Arthur A. Hurwitz, National Cancer Institute/National Institutes of Health, Frederick Cancer Research Facility, Building 567, Room 209, Frederick, MD 21701. E-mail address: hurwitza{at}mail.nih.gov

³ Abbreviations used in this paper: Treg, regulatory T cell; LN, lymph node; TAg, tumor Ag; TcR-I, tumor-specific CD8⁺ T cell; TcR-II, tumor-specific CD4+ T cell; TRAMP, transgenic adenocarcinoma of the mouse prostate; TRP, tyrosinase-related protein; WT, wild type.

⁴ The online version of this article contains supplemental material.