Vaccine-Stimulated, Adoptively Transferred CD8+ T Cells Traffic Indiscriminately and Ubiquitously while Mediating Specific Tumor Destruction1
| Autor: | Palmer, Douglas C., Balasubramaniam, Sanjeeve, Hanada, Ken-ichi, Wrzesinski, Claudia, Yu, Zhiya, Farid, Shahram, Theoret, Marc R., Hwang, Leroy N., Klebanoff, Christopher A., Gattinoni, Luca, Goldstein, Allan L., Yang, James C., Restifo, Nicholas P. |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Cytotoxicity
Immunologic Membrane Glycoproteins Fibrosarcoma Melanoma Experimental Mice Transgenic CD8-Positive T-Lymphocytes Lymphocyte Activation Cancer Vaccines Immunotherapy Adoptive Article Neoplasm Proteins Mice Inbred C57BL Mice Lymphocytes Tumor-Infiltrating Cell Movement Organ Specificity Cell Line Tumor Animals Neoplasm Transplantation Cell Proliferation gp100 Melanoma Antigen |
| 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-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: | OpenAIRE |
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