Prolonged survival of human hepatocarcinoma cells in the liver of newborn C57BL/6 mice and resulting cellular xenorejection, especially the activation of hepatic natural killer T cells.
Pathobiology
; 77(3): 115-28, 2010.
Article
em En
| MEDLINE
| ID: mdl-20516727
ABSTRACT
OBJECTIVE:
To investigate the fate of human hepatocellular carcinoma (HCC) in the livers of newborn mice and the resulting cellular rejection.METHODS:
Two HCC cell lines (HepG2 and HCCLM3) labeled with DMAHAS were orthotopically transplanted to newborn and adult mice with or without low-dose cyclosporin A (CsA) treatment (10 mg/kg). The fate of tumor xenografts was examined and the resulting cellular response was investigated.RESULTS:
Tumor xenografts survived in newborn mice for > 4 weeks, with a delayed lymphocyte infiltration mediated by CD4+ T, CD8+ T and NK1.1+ cells. In contrast, the xenografts survived in adults < 8-10 days with an acute cellular rejection by CD8+T cells, NK1.1+ cells, macrophages or neutrophils. Orthotopic transplantation of human HCC xenografts elicited a strong cytotoxic response in newborn mice (p < 0.05), and selective T/NK1.1+ cell deletion in vitro suggested that such effector cells were mainly CD8+ T cells. Moreover, tumor xenografts induced a rapid activation of hepatic natural killer T (NKT) cells in both newborn and adult mice with enhanced secretion of IL-4 and IFN-gamma in serum and subsequent NKT-like cytotoxicity. The rapid activation of NKT cells could be efficiently suppressed by low-dose CsA treatment, possibly in a CD1d-independent manner.CONCLUSION:
Our data suggest that the livers of newborn mice were more suitable for the survival of xenografts than those of adult mice. Cell-mediated tumor xenorejection in newborn mice was different from that in adults, and hepatic NKT cells may play an important role in early tumor xenorejection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Linfócitos do Interstício Tumoral
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Carcinoma Hepatocelular
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Evasão Tumoral
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Células T Matadoras Naturais
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Sobrevivência de Enxerto
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Fígado
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Neoplasias Hepáticas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article