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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0034790,
umls-concept:C0037083,
umls-concept:C0039194,
umls-concept:C0040690,
umls-concept:C0085358,
umls-concept:C0185117,
umls-concept:C1280500,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1426807,
umls-concept:C1706438,
umls-concept:C1710082,
umls-concept:C2698600,
umls-concept:C2911684
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pubmed:issue |
11
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pubmed:dateCreated |
2009-8-19
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pubmed:abstractText |
This study demonstrates that CD8+ T cells in the tumor microenvironment display reduced functionality and hyporesponsiveness. TGF-beta contributed markedly to the tumor-infiltrating CD8+ T cells' (TILs) reduced functionality, which could be reversed using a small molecule TGF-beta inhibitor. Upon T-cell receptor (TCR) activation, the activation of ITK and ERK kinases were reduced in CD8+ TILs, as compared to splenic CD8+ T cells: TGF-beta inhibitor could reverse this phenomenon. This study demonstrates for the first time the association of the Spred-1 gene, an inhibitor of the Ras/MAPK pathway, with CD8+ TILs and TGF-beta activity. Spred-1 was upregulated in CD8+ TILs and TGF-beta enhanced the expression of Spred-1 in effector/memory CD8+ T cells and not in rested/memory CD8+ T cells. Based on these findings, this study supports the hypothesis that TGF-beta mediates an inhibitory mechanism on CD8+ TILs involving TCR-signaling blockade and the upregulation of Spred-1, thus implicating Spred-1 as a potential new target for future anti-tumor immune studies.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1432-0851
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
58
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1809-18
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:19319531-Animals,
pubmed-meshheading:19319531-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19319531-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:19319531-Female,
pubmed-meshheading:19319531-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19319531-Immune Tolerance,
pubmed-meshheading:19319531-Interferon-gamma,
pubmed-meshheading:19319531-Lymphocyte Activation,
pubmed-meshheading:19319531-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:19319531-Mice,
pubmed-meshheading:19319531-Mice, Inbred C57BL,
pubmed-meshheading:19319531-Neoplasms, Experimental,
pubmed-meshheading:19319531-Phosphorylation,
pubmed-meshheading:19319531-Receptors, Antigen, T-Cell,
pubmed-meshheading:19319531-Repressor Proteins,
pubmed-meshheading:19319531-Signal Transduction,
pubmed-meshheading:19319531-Transforming Growth Factor beta
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pubmed:year |
2009
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pubmed:articleTitle |
TGF-beta modulates the functionality of tumor-infiltrating CD8+ T cells through effects on TCR signaling and Spred1 expression.
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pubmed:affiliation |
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, MSC 1750, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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