Source:http://linkedlifedata.com/resource/pubmed/id/15753372
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2005-3-8
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pubmed:abstractText |
Transforming growth factor (TGF)-beta is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells may lead to tumor evasion from the host immune surveillance and tumor progression. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. The mouse TRAMP-C2 prostate cancer cells produced large amounts of TGF-beta1 and were used as an experimental model. C57BL/6 mice were primed with irradiated TRAMP-C2 cells. CD8+ T cells were isolated from the spleen of primed animals, were expanded ex vivo, and were rendered TGF-beta insensitive by infecting with a retrovirus containing dominant-negative TGF-beta type II receptor. Results of in vitro cytotoxic assay revealed that these CD8+ T cells showed a specific and robust tumor-killing activity against TRAMP-C2 cells but were ineffective against an irrelevant tumor line, B16-F10. To determine the in vivo antitumor activity, recipient mice were challenged with a single injection of TRAMP-C2 cells for a period up to 21 days before adoptive transfer of CD8+ T cells was done. Pulmonary metastasis was either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. Results of immunofluorescent studies showed that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis in tumor cells. Furthermore, transferred tumor-reactive TGF-beta-insensitive CD8+ T cells were able to persist in tumor-bearing hosts but declined in tumor-free animals. These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for cancer therapy.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:GreenbergNorman MNM,
pubmed-author:GuoYingluY,
pubmed-author:JavonovicBorkoB,
pubmed-author:KimSeong-JinSJ,
pubmed-author:KuzelTimothyT,
pubmed-author:LeeChungC,
pubmed-author:LiuVictoriaV,
pubmed-author:ParijsLuk VanLV,
pubmed-author:PinsMichaelM,
pubmed-author:YangXimingX,
pubmed-author:ZhangQiangQ
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1761-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15753372-Adoptive Transfer,
pubmed-meshheading:15753372-Animals,
pubmed-meshheading:15753372-Apoptosis,
pubmed-meshheading:15753372-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15753372-Fluorescent Antibody Technique,
pubmed-meshheading:15753372-Genes, Dominant,
pubmed-meshheading:15753372-Green Fluorescent Proteins,
pubmed-meshheading:15753372-Lung Neoplasms,
pubmed-meshheading:15753372-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:15753372-Male,
pubmed-meshheading:15753372-Melanoma, Experimental,
pubmed-meshheading:15753372-Mice,
pubmed-meshheading:15753372-Mice, Inbred C57BL,
pubmed-meshheading:15753372-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:15753372-Prostatic Neoplasms,
pubmed-meshheading:15753372-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15753372-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:15753372-Retroviridae,
pubmed-meshheading:15753372-Skin Neoplasms,
pubmed-meshheading:15753372-Spleen,
pubmed-meshheading:15753372-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:15753372-Transfection,
pubmed-meshheading:15753372-Transforming Growth Factor beta
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pubmed:year |
2005
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pubmed:articleTitle |
Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer.
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pubmed:affiliation |
Department of Urology, Northwestern University's Feinberg School of Medicine, Chicago, Illinois 60611, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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