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Induction of Postsurgical Tumor Immunity and T-Cell Memory by a Poorly Immunogenic Tumor

Department of Microbiology and Immunology and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire

Requests for reprints: Mary Jo Turk, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756. Phone: 603-653-3549; Fax: 603-653-9952; E-mail: mary.jo.turk{at}dartmouth.edu.

The generation of protective CD8 T-cell memory against tumor-expressed self-antigens is an important but elusive goal of cancer immunotherapy. The possibility that a progressive, poorly immunogenic tumor can induce T-cell memory against self-antigens has not previously been studied. Herein, we report that growth of the poorly immunogenic B16 melanoma in the absence of regulatory T cells (T_reg) generates CD8 T-cell responses that develop into functional memory after the tumor has been surgically excised. Tumor-primed memory T cells recognized melanocyte differentiation antigens TRP-2/DCT and gp100 and persisted for as long as 5 months following surgical tumor excision. Phenotypic analysis showed that these cells develop into both central and effector memory T-cell subsets, which produce IFN- and interleukin-2 on reencounter with antigen. Most importantly, tumor-primed memory T cells mediated the rejection of intradermal and systemically disseminated challenge tumors given 30 to 60 days following surgery. Tumor-excised mice also developed autoimmune vitiligo, showing that T_reg cells prevent tissue-specific autoimmunity in tumor-bearing hosts. This study establishes that T_reg depletion in tumor-bearing hosts drives the natural development of protective T-cell memory. Generating such responses may aid in the clinical management of tumor recurrence and metastasis following surgery. [Cancer Res 2007;67(13):6468–76]

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				A. L. Cote, E. J. Usherwood, and M. J. Turk Tumor-Specific T-Cell Memory: Clearing the Regulatory T-Cell Hurdle Cancer Res., March 15, 2008; 68(6): 1614 - 1617. [Abstract] [Full Text] [PDF]