Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination
AUTOR(ES)
Klebanoff, Christopher A.
FONTE
American Society of Hematology
RESUMO
Naive and memory CD8+ T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8+ T cells (TEM) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated TEM cells. This programmed response was associated with an interval of antigen-independent interferon-γ (IFN-γ) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2Db on responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN-γ entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-γ had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8+ T cells and have major implications for the design of current adoptive-cell transfer trials.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2738567Documentos Relacionados
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