| Autor: |
Palmer DC; National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. palmerd@mail.nih.gov, Balasubramaniam S, Hanada K, Wrzesinski C, Yu Z, Farid S, Theoret MR, Hwang LN, Klebanoff CA, Gattinoni L, Goldstein AL, Yang JC, Restifo NP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Dec 15; Vol. 173 (12), pp. 7209-16. |
| DOI: |
10.4049/jimmunol.173.12.7209 |
| Abstrakt: |
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-gamma, 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: |
MEDLINE |
| Externí odkaz: |
|
