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rdf:type |
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lifeskim:mentions |
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0039194,
umls-concept:C0070410,
umls-concept:C0205173,
umls-concept:C0205224,
umls-concept:C0376518,
umls-concept:C0600138,
umls-concept:C0812246,
umls-concept:C1456820,
umls-concept:C1718423
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pubmed:issue |
4
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pubmed:dateCreated |
2003-2-7
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pubmed:abstractText |
We have recently shown that effector T cells (T(E)) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, T(E) deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T(E) mediated complete tumor regression and cured wild-type animals with established pulmonary metastases of the B16BL6-D5 (D5) melanoma cell line. PKO/GKO T(E) also mediated tumor regression in D5 tumor-bearing PKO, GKO, or PKO/GKO recipients, although in PKO/GKO recipients efficacy was reduced. PKO/GKO T(E) exhibited tumor-specific TNF-alpha production and cytotoxicity in a 24-h assay, which was blocked by the soluble TNFRII-human IgG fusion protein (TNFRII:Fc). Blocking TNF in vivo by administering soluble TNFR II fusion protein (TNFRII:Fc) significantly reduced the therapeutic efficacy of PKO/GKO, but not wild-type T(E). This study identifies perforin, IFN-gamma, and TNF as a critical triad of effector molecules that characterize therapeutic antitumor T cells. These insights could be used to monitor and potentially tune the immune response to cancer vaccines.
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pubmed:grant |
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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/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fc Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Perforin,
http://linkedlifedata.com/resource/pubmed/chemical/Pore Forming Cytotoxic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2004-13
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12574370-Adoptive Transfer,
pubmed-meshheading:12574370-Animals,
pubmed-meshheading:12574370-Antigens, CD,
pubmed-meshheading:12574370-Binding, Competitive,
pubmed-meshheading:12574370-Cancer Vaccines,
pubmed-meshheading:12574370-Cells, Cultured,
pubmed-meshheading:12574370-Cytotoxicity, Immunologic,
pubmed-meshheading:12574370-Epitopes, T-Lymphocyte,
pubmed-meshheading:12574370-Immunoglobulin Fc Fragments,
pubmed-meshheading:12574370-Injections, Intraperitoneal,
pubmed-meshheading:12574370-Injections, Subcutaneous,
pubmed-meshheading:12574370-Interferon-gamma,
pubmed-meshheading:12574370-Lung Neoplasms,
pubmed-meshheading:12574370-Melanoma, Experimental,
pubmed-meshheading:12574370-Membrane Glycoproteins,
pubmed-meshheading:12574370-Mice,
pubmed-meshheading:12574370-Mice, Inbred C57BL,
pubmed-meshheading:12574370-Mice, Knockout,
pubmed-meshheading:12574370-Perforin,
pubmed-meshheading:12574370-Pore Forming Cytotoxic Proteins,
pubmed-meshheading:12574370-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12574370-Receptors, Tumor Necrosis Factor, Type II,
pubmed-meshheading:12574370-Recombinant Fusion Proteins,
pubmed-meshheading:12574370-T-Lymphocyte Subsets,
pubmed-meshheading:12574370-T-Lymphocytes, Regulatory,
pubmed-meshheading:12574370-Tumor Cells, Cultured,
pubmed-meshheading:12574370-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells.
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pubmed:affiliation |
Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan Street, Portland, OR 97213, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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