E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction.
Proc Natl Acad Sci U S A
; 106(15): 6250-5, 2009 Apr 14.
Article
en En
| MEDLINE
| ID: mdl-19332800
ABSTRACT
Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Emu-TCL1 transgenic mouse model. With development of leukemia, Emu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Emu-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfocitos T
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Leucemia Linfocítica Crónica de Células B
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Proteínas Proto-Oncogénicas
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Modelos Animales de Enfermedad
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Inmunoterapia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos