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Blood, 1 October 2004, Vol. 104, No. 7, pp. 1970-1978.
Prepublished online as a Blood First Edition Paper on June 8, 2004; DOI 10.1182/blood-2004-02-0525.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Quiescent phenotype of tumor-specific CD8+ T cells following immunization
Vladia Monsurrò,
Ena Wang,
Yoshisha Yamano,
Stephen A. Migueles,
Monica C. Panelli,
Kina Smith,
Dirk Nagorsen,
Mark Connors,
Steven Jacobson, and
Francesco M. Marincola
From the Immunogenetics Section of the Department of Transfusion Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD; Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke (NINDS), NIH, Bethesda, MD; and Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD.
In a human melanoma model of tumor antigen (TA)–based immunization, we tested the functional status of TA-specific CD8+ cytotoxic T lymphocytes. A "quiescent" phenotype lacking direct ex vivo cytotoxic and proliferative potential was identified that was further characterized by comparing its transcriptional profile to that of TA-specific T cells sensitized in vitro by exposure to the same TA and the T-cell growth factor interleukin 2 (IL-2). Quiescent circulating tumor-specific CD8+ T cells were deficient in expression of genes associated with T-cell activation, proliferation, and effector function. This quiescent status may explain the observed lack of correlation between the presence of circulating immunization-induced lymphocytes and tumor regression. In addition, the activation of TA-specific T cells by in vitro antigen recall and IL-2 suggests that a complete effector phenotype might be reinstated in vivo to fulfill the potential of anticancer vaccine protocols.
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