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

被引:59
|
作者
Monsurrò, V
Wang, E
Yamano, Y
Migueles, SA
Panelli, MC
Smith, K
Nagorsen, D
Connors, M
Jacobson, S
Marincola, FM
机构
[1] NIH, Dept Transfus Med, Clin Ctr, Immunogenet Sect, Bethesda, MD 20892 USA
[2] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA
[3] NIAID, Lab Immunoregulat, NIH, Bethesda, MD USA
关键词
D O I
10.1182/blood-2004-02-0525
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2004 by The American Society of Hematology.
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页码:1970 / 1978
页数:9
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