Source:http://linkedlifedata.com/resource/pubmed/id/19592642
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2009-7-21
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pubmed:abstractText |
Elimination of peripheral tumors by adoptively transferred tumor-specific T cells may require killing of cancer cells and tumor stromal cells. Tumor Ags are cross-presented on stromal cells, resulting in direct cytotoxic T cell (CTL) killing of both Ag-expressing cancer cells and stromal cells. Indirect killing of Ag loss variant cells also occurs. We show here that similar processes occur in a brain tumor stromal environment. We used murine cancer cell lines that express high or low levels of a peptide Ag, SIYRYYGL (SIY), recognized by transgenic 2C CD8(+) T cells. The two cell lines are killed with equivalent efficiency by 2C T cells in vitro. Following adoptive transfer of 2C T cells into mice with established SIY-Hi or SIY-Lo brain tumors, tumors of both types regressed, but low-Ag-expressing tumors recurred. High-Ag-expressing tumors contained CD11b(+) cells cross-presenting SIY peptide and were completely eliminated by 2C T cells. To further test the role of cross-presentation, RAG1(-/-) H-2(b) mice were infused with H-2(k) tumor cells expressing high levels of SIY peptide. Adoptively transferred 2C T cells are able to kill cross-presenting H-2(b) stromal cells but not H-2(k) tumor cells. In peripheral models, this paradigm led to a small static tumor. In the brain, activated 2C T cells were able to kill cross-presenting CD11b(+) cells and completely eliminate the H-2(k) tumors in most mice. Targeting brain tumor stroma or increasing Ag shedding from tumor cells to enhance cross-presentation may improve the clinical success of T cell adoptive therapies.
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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 |
Aug
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1828-37
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pubmed:meshHeading |
pubmed-meshheading:19592642-Adoptive Transfer,
pubmed-meshheading:19592642-Animals,
pubmed-meshheading:19592642-Antigens, Neoplasm,
pubmed-meshheading:19592642-Brain Neoplasms,
pubmed-meshheading:19592642-Cell Line, Tumor,
pubmed-meshheading:19592642-Cross-Priming,
pubmed-meshheading:19592642-Cytotoxicity, Immunologic,
pubmed-meshheading:19592642-Mice,
pubmed-meshheading:19592642-Mice, Knockout,
pubmed-meshheading:19592642-Recurrence,
pubmed-meshheading:19592642-Stromal Cells,
pubmed-meshheading:19592642-T-Lymphocytes, Cytotoxic
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pubmed:year |
2009
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pubmed:articleTitle |
Recurrence of intracranial tumors following adoptive T cell therapy can be prevented by direct and indirect killing aided by high levels of tumor antigen cross-presented on stromal cells.
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pubmed:affiliation |
University of Illinois, Urbana-Champaign, Urbana, IL 61801, 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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