Linked Life Data

11668505

Source:http://linkedlifedata.com/resource/pubmed/id/11668505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-10-22
pubmed:abstractText
Cell surface expression of HLA class I/peptide complexes on tumor cells is a key step in the generation of T-cell-based immune responses. Several genetic defects underlying the lack of HLA class I expression have been characterized. Here we describe another molecular mechanism that accounts for the complete absence of HLA class I molecule expression in a tumor line (MSR3-mel) derived from a melanoma patient. Hypermethylation of the MSR3-mel DNA, specifically of HLA-A and -B genes, was identified, which resulted in loss of HLA class I heavy chain transcription. Treatment of MSR3-mel cells with the demethylating agent 5'-aza-2'-deoxycytidine (DAC) allowed HLA-A and -B transcription, restoring cell surface expression of HLA class I antigens and tumor cell recognition by MAGE-specific cytotoxic T lymphocytes. The MSR3-mel line was obtained from a metastatic lesion of a nonresponding patient undergoing MAGE-3.A1 T-cell-based peptide immunotherapy. It is tempting to speculate that the hypermethylation-induced lack of HLA class I expression is the cause of the impaired response to vaccination. This study provides the first evidence that DNA hypermethylation is used by human neoplastic cells to switch off HLA class I genes, thus providing a new route of escape from immune recognition.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
243-51
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Rexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2'-deoxycytidine treatment.
pubmed:affiliation
Servicio de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Granada, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't