Source:http://linkedlifedata.com/resource/pubmed/id/15294960
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-8-5
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pubmed:abstractText |
Radiation is generally considered to be an immunosuppressive agent that acts by killing radiosensitive lymphocytes. In this study, we demonstrate the noncytotoxic effects of ionizing radiation on MHC class I Ag presentation by bone marrow-derived dendritic cells (DCs) that have divergent consequences depending upon whether peptides are endogenously processed and loaded onto MHC class I molecules or are added exogenously. The endogenous pathway was examined using C57BL/6 murine DCs transduced with adenovirus to express the human melanoma/melanocyte Ag recognized by T cells (AdVMART1). Prior irradiation abrogated the ability of AdVMART1-transduced DCs to induce MART-1-specific T cell responses following their injection into mice. The ability of these same DCs to generate protective immunity against B16 melanoma, which expresses murine MART-1, was also abrogated by radiation. Failure of AdVMART1-transduced DCs to generate antitumor immunity following irradiation was not due to cytotoxicity or to radiation-induced block in DC maturation or loss in expression of MHC class I or costimulatory molecules. Expression of some of these molecules was affected, but because irradiation actually enhanced the ability of DCs to generate lymphocyte responses to the peptide MART-1(27-35) that is immunodominant in the context of HLA-A2.1, they were unlikely to be critical. The increase in lymphocyte reactivity generated by irradiated DCs pulsed with MART-1(27-35) also protected mice against growth of B16-A2/K(b) tumors in HLA-A2.1/K(b) transgenic mice. Taken together, these results suggest that radiation modulates MHC class I-mediated antitumor immunity by functionally affecting DC Ag presentation pathways.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/MART-1 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/MLANA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mlana protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2462-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15294960-Animals,
pubmed-meshheading:15294960-Antigen Presentation,
pubmed-meshheading:15294960-Antigens, Neoplasm,
pubmed-meshheading:15294960-Cell Line, Tumor,
pubmed-meshheading:15294960-Dendritic Cells,
pubmed-meshheading:15294960-Histocompatibility Antigens Class I,
pubmed-meshheading:15294960-Humans,
pubmed-meshheading:15294960-Immunoassay,
pubmed-meshheading:15294960-Lymphocyte Activation,
pubmed-meshheading:15294960-MART-1 Antigen,
pubmed-meshheading:15294960-Melanoma, Experimental,
pubmed-meshheading:15294960-Mice,
pubmed-meshheading:15294960-Neoplasm Proteins,
pubmed-meshheading:15294960-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15294960-T-Lymphocytes,
pubmed-meshheading:15294960-Transduction, Genetic
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pubmed:year |
2004
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pubmed:articleTitle |
Ionizing radiation affects human MART-1 melanoma antigen processing and presentation by dendritic cells.
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pubmed:affiliation |
Department of Radiation Oncology, Division of Surgical Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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