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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2005-3-4
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pubmed:abstractText |
Dendritic cells (DCs) are being evaluated for cancer immunotherapy due to their unique ability to induce tumor-directed T-cell responses. Here we report that the type of human DC, the mode of activation, and the strategy for delivery of antigen are 3 critical factors for efficient stimulation of tumor-specific CD8+ and CD4+ T cells. Only CD1c+ blood DCs and monocyte-derived DCs (MoDCs) were capable of presenting epitopes of the full-length tumor antigen NY-ESO-1 on both major histocompatibility complex (MHC) class I (cross-presentation) and MHC II, whereas plasmacytoid DCs were limited to MHC II presentation. Cross-presentation was inefficient for soluble protein, but highly efficient for antigen-antibody immune complexes (NY-ESO-1/IC) and for protein formulated with ISCOMATRIX adjuvant (NY-ESO-1/IMX). DC activation with CD40L further enhanced cross-presentation efficiency. The mode of antigen delivery was found to be a determining factor for cytosolic proteolysis by DCs. Immune complexes (ICs) targeted a slow, proteasome-dependent cross-presentation pathway, whereas ISCOMATRIX (IMX) targeted a fast, proteasome-independent pathway. Both cross-presentation pathways resulted in a long-lived, T-cell stimulatory capacity, which was maintained for several days longer than for DCs pulsed with peptide. This may provide DCs with ample opportunities for sensitizing tumor-specific T cells against a broad array of tumor antigen epitopes in lymph nodes.
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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/Adjuvants, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Antigen-Antibody Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/CTAG1B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/ISCOMATRIX,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Saponins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:CebonJonathanJ,
pubmed-author:ChenQiyuanQ,
pubmed-author:ChenWeisanW,
pubmed-author:DavisIan DID,
pubmed-author:DraneDebbieD,
pubmed-author:GreenSimonS,
pubmed-author:JenderekCorinnaC,
pubmed-author:MaraskovskyEugeneE,
pubmed-author:MiloradovicLenaL,
pubmed-author:SchnurrMaxM,
pubmed-author:ShinAmandaA,
pubmed-author:ShortmanKenK,
pubmed-author:ToyTraceyT,
pubmed-author:VilladangosJoseJ
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2465-72
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15546948-Adjuvants, Immunologic,
pubmed-meshheading:15546948-Antigen Presentation,
pubmed-meshheading:15546948-Antigen-Antibody Complex,
pubmed-meshheading:15546948-Antigens, Neoplasm,
pubmed-meshheading:15546948-CD4-Positive T-Lymphocytes,
pubmed-meshheading:15546948-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15546948-Cancer Vaccines,
pubmed-meshheading:15546948-Cells, Cultured,
pubmed-meshheading:15546948-Cholesterol,
pubmed-meshheading:15546948-Dendritic Cells,
pubmed-meshheading:15546948-Drug Combinations,
pubmed-meshheading:15546948-Epitopes, T-Lymphocyte,
pubmed-meshheading:15546948-Female,
pubmed-meshheading:15546948-Histocompatibility Antigens Class I,
pubmed-meshheading:15546948-Histocompatibility Antigens Class II,
pubmed-meshheading:15546948-Humans,
pubmed-meshheading:15546948-Lymph Nodes,
pubmed-meshheading:15546948-Male,
pubmed-meshheading:15546948-Melanoma,
pubmed-meshheading:15546948-Membrane Proteins,
pubmed-meshheading:15546948-Monocytes,
pubmed-meshheading:15546948-Phospholipids,
pubmed-meshheading:15546948-Plasma Cells,
pubmed-meshheading:15546948-Proteasome Endopeptidase Complex,
pubmed-meshheading:15546948-Saponins
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pubmed:year |
2005
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pubmed:articleTitle |
Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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