Functional up-regulation of human leukocyte antigen class I antigens expression by 5-aza-2'-deoxycytidine in cutaneous melanoma: immunotherapeutic implications.
Clin Cancer Res
; 13(11): 3333-8, 2007 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-17545540
ABSTRACT
PURPOSE:
To investigate the potential of the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) to improve the effectiveness of immunotherapeutic approaches against melanocyte differentiation antigens. EXPERIMENTALDESIGN:
The effect of 5-aza-CdR on the constitutive expression of gp100 was investigated in 11 human melanoma cell lines by real-time reverse transcription-PCR and indirect immunofluorescence (IIF) analyses. 5-aza-CdR-mediated changes in the levels of expression of human leukocyte antigen (HLA) class I antigens and HLA-A2 allospecificity, intercellular adhesion molecule-1 (ICAM-1), and leukocyte-function-associated antigen-3 were investigated by IIF analysis on melanoma cells under study. The recognition of gp100-positive Mel 275 melanoma cells, treated or not with 5-aza-CdR, by HLA-A2-restricted gp100((209-217))-specific CTL was investigated by (51)Cr-release assays, IFN-gamma release and IFN-gamma ELISPOT assays.RESULTS:
The constitutive expression of gp100 was not affected by 5-aza-CdR on all melanoma cells investigated. Compared with untreated cells, the exposure of Mel 275 melanoma cells to 5-aza-CdR significantly (P < 0.05) up-regulated their expression of HLA class I antigens and of ICAM-1. These phenotypic changes significantly (P < 0.05) increased the lysis of 5-aza-CdR-treated Mel 275 melanoma cells by gp100-specific CTL and increased their IFN-gamma release. 5-aza-CdR treatment of Mel 275 cells also induced a higher number of gp100-specific CTL to secrete IFN-gamma.CONCLUSIONS:
Treatment with 5-aza-CdR improves the recognition of melanoma cells by gp100-specific CTL through the up-regulation of HLA class I antigens expression; ICAM-1 also contributes to this phenomenon. These findings highlight a broader range of therapeutic implications of 5-aza-CdR when used in association with active or adoptive immunotherapeutic approaches against a variety of melanoma-associated antigens.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Azacitidina
/
Linfócitos T Citotóxicos
/
Antígenos de Histocompatibilidade Classe I
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Regulação Neoplásica da Expressão Gênica
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Imunoterapia
/
Melanoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article