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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2009-3-20
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pubmed:abstractText |
Clinical responses of solid tumors after allogeneic human leukocyte antigen-matched stem cell transplantation (SCT) often coincide with severe graft-versus-host disease (GVHD). Targeting minor histocompatibility antigens (mHags) with hematopoiesis- and cancer-restricted expression, for example, HA-1, may allow boosting the antitumor effect of allogeneic SCT without risking severe GVHD. The mHag HA-1 is aberrantly expressed in cancers of most entities. However, an estimated 30% to 40% of solid tumors do not express HA-1 (ie, are HA-1(neg)) and cannot be targeted by HA-1-specific immunotherapy. Here, we investigated the transcriptional regulation of HA-1 gene expression in cancer. We found that DNA hypermethylation in the HA-1 promoter region is closely associated with the absence of HA-1 gene expression in solid tumor cell lines. Moreover, we detected HA-1 promoter hypermethylation in primary cancers. The hypomethylating agent 5-aza-2'-deoxycytidine induced HA-1 expression only in HA-1(neg) tumor cells and sensitized them for recognition by HA-1-specific cytotoxic T lymphocytes. Contrarily, the histone deacetylation inhibitor trichostatin A induced HA-1 expression both in some HA-1(neg) tumor cell lines and in normal nonhematopoietic cells. Our data suggest that promoter hypermethylation contributes to the HA-1 gene regulation in tumors. Hypomethylating drugs might extend the safe applicability of HA-1 as an immunotherapeutic target on solid tumors after allogeneic SCT.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/DNA (Cytosine-5-)-Methyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA...,
http://linkedlifedata.com/resource/pubmed/chemical/HA-1 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Histones,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Minor Histocompatibility Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/decitabine,
http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:AghaiZoharaZ,
pubmed-author:BloklandElsE,
pubmed-author:BruijnJan AJA,
pubmed-author:GoulmyElsE,
pubmed-author:HalfwerkHansH,
pubmed-author:HambachLotharL,
pubmed-author:LingKam-WingKW,
pubmed-author:PoolJosJ,
pubmed-author:TankeHans JHJ,
pubmed-author:WielesBrigitteB,
pubmed-author:van BovenHesterH
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
113
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2715-22
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pubmed:meshHeading |
pubmed-meshheading:19096014-Acetylation,
pubmed-meshheading:19096014-Antigens, Neoplasm,
pubmed-meshheading:19096014-Azacitidine,
pubmed-meshheading:19096014-Cell Line, Tumor,
pubmed-meshheading:19096014-CpG Islands,
pubmed-meshheading:19096014-DNA, Neoplasm,
pubmed-meshheading:19096014-DNA (Cytosine-5-)-Methyltransferase,
pubmed-meshheading:19096014-DNA Methylation,
pubmed-meshheading:19096014-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19096014-Gene Silencing,
pubmed-meshheading:19096014-Histones,
pubmed-meshheading:19096014-Humans,
pubmed-meshheading:19096014-Hydroxamic Acids,
pubmed-meshheading:19096014-Immunotherapy,
pubmed-meshheading:19096014-Minor Histocompatibility Antigens,
pubmed-meshheading:19096014-Neoplasm Proteins,
pubmed-meshheading:19096014-Neoplasms,
pubmed-meshheading:19096014-Oligopeptides,
pubmed-meshheading:19096014-Promoter Regions, Genetic,
pubmed-meshheading:19096014-Protein Processing, Post-Translational,
pubmed-meshheading:19096014-RNA, Messenger,
pubmed-meshheading:19096014-RNA, Neoplasm,
pubmed-meshheading:19096014-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:19096014-Transcription, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
Hypomethylating drugs convert HA-1-negative solid tumors into targets for stem cell-based immunotherapy.
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pubmed:affiliation |
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. l.w.h.hambach@lumc.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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