Quiescent phenotype of tumor-specific CD8+ T cells following immunization

V Monsurṛ, E Wang, Y Yamano, SA Migueles… - Blood, 2004 - ashpublications.org
V Monsurṛ, E Wang, Y Yamano, SA Migueles, MC Panelli, K Smith, D Nagorsen…
Blood, 2004ashpublications.org
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 …
Abstract
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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