Enhancement of human melanoma antigen expression by IFN-beta.
J Immunol
; 179(4): 2134-42, 2007 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-17675472
ABSTRACT
Although many immunotherapeutic investigations have focused on improving the effector limb of the antitumor response, few studies have addressed preventing the loss of tumor-associated Ag (TAA) expression, associated with immune escape by tumors. We found that TAA loss from human melanomas usually results from reversible gene down-regulation, rather than gene deletion or mutation. Previously, we showed that inhibitors of MAPK-signaling pathways up-regulate TAA expression in melanoma cell lines. We have now identified IFN-beta as an additional stimulus to TAA expression, including Melan-A/MART-1, gp100, and MAGE-A1. IFN-beta (but neither IFN-alpha nor IFN-gamma) augmented both protein and mRNA expression of melanocytic TAA in 15 melanoma lines (irrespective of initial Ag-expression levels). Treatment of low Ag melanoma lines with IFN-beta increased expression of melanocyte-lineage Ags, inducing susceptibility to lysis by specific CTLs. Treatment with IFN-beta also enhances expression of class I HLA molecules, thereby inducing both nominal TAA and the presenting HLA molecule. Data from fluorescent cellular reporter systems demonstrated that IFN-beta triggers promoter activation, resulting in augmentation of Ag expression. In addition to enhancing TAA expression in melanomas, IFN-beta also stimulated expression of the melanocytic Ag gp100 in cells of other neural crest-derived tumor lines (gliomas) and certain unrelated tumors. Because IFN-beta is already approved for human clinical use in other contexts, it may prove useful as a cotreatment for augmenting tumor Ag expression during immunotherapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Interferón beta
/
Escape del Tumor
/
Melanoma
/
Antígenos de Neoplasias
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos