The dysfunction and abnormal signaling pathway of dendritic cells loaded by tumor antigen can be overcome by neutralizing VEGF in multiple myeloma.
Leuk Res
; 33(5): 665-70, 2009 May.
Article
en En
| MEDLINE
| ID: mdl-18922577
ABSTRACT
We investigated whether dendritic cells (DCs) from multiple myeloma (MM) patients were affected by loading tumor antigens and whether the defective DC function associated with MM could be overcome by the neutralization of VEGF. MM-specific DCs were generated by loading tumor lysates from myeloma cells at diagnosis or relapsed/progressive state, respectively. DCs loaded with tumor lysates showed lower phenotypic maturation, less T cell stimulatory capacity, less cytotoxic T lymphocyte activities, and highly abnormal cytokine secretions of IL-6 and IL-12, compared to myeloma lysate-unloaded DCs. The levels of VEGF, phospho-STAT3 and phospho-ERK1/2 in DCs were significantly higher with loading myeloma lysates. After the neutralization of VEGF activity, the DC function, signal transduction and cytokine production returned to normal. The defective function of DC in patients with MM is significantly affected by loading tumor antigens, correlating with abnormal STAT3 and the NF-kappaB signaling pathway, and neutralization of VEGF can overcome this DC dysfunction through the elimination of abnormal signal transduction.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Transducción de Señal
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Factor A de Crecimiento Endotelial Vascular
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Mieloma Múltiple
Límite:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Leuk Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Corea del Sur