Source:http://linkedlifedata.com/resource/pubmed/id/18292536
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2008-2-22
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pubmed:abstractText |
Alterations to the tumor microenvironment following localized irradiation may influence the effectiveness of subsequent immunotherapy. The objective of this study was to determine how IFN-gamma influences the inflammatory response within this dynamic environment following radiotherapy. B16/OVA melanoma cells were implanted into C57BL/6 (wild-type (WT)) and IFN-gamma-deficient (IFN-gamma-/-) mice. Seven days after implantation, mice received 15 Gy of localized tumor irradiation and were assessed 7 days later. Irradiation up-regulated the expression of VCAM-1 on the vasculature of tumors grown in WT but not in IFN-gamma-/- mice. Levels of the IFN-gamma-inducible chemokines MIG and IFN-gamma-inducible protein 10 were decreased in irradiated tumors from IFN-gamma-/- mice compared with WT. In addition to inducing molecular cues necessary for T cell infiltration, surface MHC class I expression is also up-regulated in response to IFN-gamma produced after irradiation. The role of IFN-gamma signaling in tumor cells on class I expression was tested using B16/OVA cells engineered to overexpress a dominant negative mutant IFN-gamma receptor (B16/OVA/DNM). Following implantation and treatment, expression of surface class I on tumor cells in vivo was increased in B16/OVA, but not in B16/OVA/DNM tumors, suggesting IFN-gamma acts directly on tumor cells to induce class I up-regulation. These increases in MHC class I expression correlated with greater levels of activated STAT1. Thus, IFN-gamma is instrumental in creating a tumor microenvironment conducive for T cell infiltration and tumor cell target recognition.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
180
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3132-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18292536-Animals,
pubmed-meshheading:18292536-Cell Line, Tumor,
pubmed-meshheading:18292536-Cell Movement,
pubmed-meshheading:18292536-Gamma Rays,
pubmed-meshheading:18292536-Histocompatibility Antigens Class I,
pubmed-meshheading:18292536-Interferon-gamma,
pubmed-meshheading:18292536-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:18292536-Melanoma, Experimental,
pubmed-meshheading:18292536-Mice,
pubmed-meshheading:18292536-Mice, Inbred C57BL,
pubmed-meshheading:18292536-Mice, Knockout,
pubmed-meshheading:18292536-Mice, Transgenic,
pubmed-meshheading:18292536-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:18292536-Up-Regulation
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pubmed:year |
2008
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pubmed:articleTitle |
Radiation-induced IFN-gamma production within the tumor microenvironment influences antitumor immunity.
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pubmed:affiliation |
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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