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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-8-17
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pubmed:abstractText |
One mechanism by which potentially immunogenic tumors evade the immune response is production of immunosuppressive factors. The murine mammary sarcoma EMT6 has previously been demonstrated to inhibit the proliferation of B-cells, suggesting that this tumor produces immunosuppressive factors. Here, we show that supernatant from EMT6 inhibits the development of cytotoxic T-lymphocytes (CTLs) and that this inhibition can be reversed by addition of recombinant interleukin (IL)-2. Furthermore, we show that EMT6 produces high levels of the immunosuppressant factor transforming growth factor (TGF)-beta. To determine if the T-cell growth factor IL-2 within the tumor microenvironment could reverse the immunosuppressive effect of EMT6, we transfected EMT6 with an expression vector containing the cDNA for murine IL-2 under the control of the beta-actin promoter. These transfectants produce significant levels of IL-2 (26 U/ml). EMT6/IL-2 is rejected by mice at 100-fold higher challenge than are parental cells or control transfectants (neomycin resistance only). Thy-1-expressing cells purified from EMT6/IL-2 tumors show greater cytotoxicity against the parental EMT6 cells than do those from the control transfectant. Thus, IL-2 can reverse the effects of TGF-beta on development and/or proliferation of CTL reactive with EMT6, allowing the establishment of mature effectors in vivo. This has significant implications for the development of CTL and immunotherapy for immunosuppressive tumors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1067-5582
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
155-64
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8032538-Animals,
pubmed-meshheading:8032538-Graft Rejection,
pubmed-meshheading:8032538-Interleukin-2,
pubmed-meshheading:8032538-Lymphocyte Activation,
pubmed-meshheading:8032538-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:8032538-Mice,
pubmed-meshheading:8032538-Mice, Inbred BALB C,
pubmed-meshheading:8032538-Mice, Inbred C57BL,
pubmed-meshheading:8032538-Neoplasm Transplantation,
pubmed-meshheading:8032538-Sarcoma, Experimental,
pubmed-meshheading:8032538-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:8032538-Transfection,
pubmed-meshheading:8032538-Transforming Growth Factor beta
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pubmed:year |
1994
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pubmed:articleTitle |
Transfection of transforming growth factor-beta producing tumor EMT6 with interleukin-2 elicits tumor rejection and tumor reactive cytotoxic T-lymphocytes.
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pubmed:affiliation |
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, New York 14642.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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