Vaccine-Stimulated, Adoptively Transferred CD8+ T Cells Traffic Indiscriminately and Ubiquitously while Mediating Specific Tumor Destruction
| Autor: | Claudia Wrzesinski, Shahram Farid, Nicholas P. Restifo, Sanjeeve Balasubramaniam, Marc R. Theoret, Douglas C. Palmer, Leroy N. Hwang, James Chih-Hsin Yang, Christopher A. Klebanoff, Luca Gattinoni, Ken-ichi Hanada, Allan L. Goldstein, Zhiya Yu |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 173:7209-7216 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | It has been suggested that antitumor T cells specifically traffic to the tumor site, where they effect tumor destruction. To test whether tumor-reactive CD8+ T cells specifically home to tumor, we assessed the trafficking of gp100-specific pmel-1 cells to large, vascularized tumors that express or do not express the target Ag. Activation of tumor-specific CD8+ pmel-1 T cells with IL-2 and vaccination with an altered peptide ligand caused regression of gp100-positive tumors (B16), but not gp100-negative tumors (methylcholanthrene 205), implanted on opposing flanks of the same mouse. Surprisingly, we found approximately equal and very large numbers of pmel-1 T cells (>25% of all lymphocytes) infiltrating both Ag-positive and Ag-negative tumors. We also found evidence of massive infiltration and proliferation of activated antitumor pmel-1 cells in a variety of peripheral tissues, including lymph nodes, liver, spleen, and lungs, but not peripheral blood. Most importantly, evidence for T cell function, as measured by production of IFN-γ, release of perforin, and activation of caspase-3 in target cells, was confined to Ag-expressing tumor. We thus conclude that CD8+ T cell-mediated destruction of tumor is the result of specific T cell triggering at the tumor site. The ability to induce ubiquitous homing and specific tumor destruction may be important in the case of noninflammatory metastatic tumor foci. |
| Databáze: | OpenAIRE |
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