Quiescent phenotype of tumor-specific CD8+ T cells following immunization.
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.
Monsurrò
Vladia
V
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Wang
Ena
E
Yamano
Yoshisha
Y
Migueles
Stephen A
SA
Panelli
Monica C
MC
Smith
Kina
K
Nagorsen
Dirk
D
Connors
Mark
M
Jacobson
Steven
S
Marincola
Francesco M
FM
D000970:Antineoplastic Agents / Q000494:pharmacology; D016827:CD8 Antigens / Q000737:chemistry; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002469:Cell Separation; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation; D008545:Melanoma / Q000097:blood; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic
D000970:Antineoplastic Agents; D016827:CD8 Antigens; D000939:Epitopes; D010455:Peptides