PLZF confers effector functions to donor T cells that preserve graft-versus-tumor effects while attenuating GVHD.
Cancer Res
; 73(15): 4687-96, 2013 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-23733752
ABSTRACT
Efforts to limit GVHD mediated by alloreactive donor T cells after allogeneic bone marrow transplantation are limited by a concomitant decrease in graft-versus-tumor (GVT) activity and increased possibilities of tumor relapse. Using a novel approach, we adoptively transferred conventional T cells expressing the transcription factor promyelocytic leukemia zinc finger (PLZF), which confers effector properties resembling invariant natural killer T cells, such as copious production of cytokines under suboptimal stimulation. PLZF expression in T-cell allografts attenuates expansion of alloreactive T cells, leading to lower GVHD. Intact alloreactivity-driven antitumor cytokine responses result in preserved GVT effects, leading to improved survival. Our findings suggest that therapy with PLZF-overexpressing T cells would result in overall improved outcomes due to less GVHD and intact GVT effects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Efeito Enxerto vs Tumor
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Fatores de Transcrição Kruppel-Like
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Doença Enxerto-Hospedeiro
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Neoplasias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article