Linked Life Data

19592642

Source:http://linkedlifedata.com/resource/pubmed/id/19592642

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pubmed-article:19592642pubmed:dateCreated2009-7-21lld:pubmed
pubmed-article:19592642pubmed:abstractTextElimination 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.lld:pubmed
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pubmed-article:19592642pubmed:authorpubmed-author:RoyEdward JEJlld:pubmed
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pubmed-article:19592642pubmed:pagination1828-37lld:pubmed
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pubmed-article:19592642pubmed:year2009lld:pubmed
pubmed-article:19592642pubmed:articleTitleRecurrence 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.lld:pubmed
pubmed-article:19592642pubmed:affiliationUniversity of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.lld:pubmed
pubmed-article:19592642pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:19592642pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:19592642pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed