Vaccine-stimulated, adoptively transferred CD8+ T cells traffic indiscriminately and ubiquitously while mediating specific tumor destruction

DC Palmer, S Balasubramaniam, K Hanada… - The Journal of …, 2004 - journals.aai.org
DC Palmer, S Balasubramaniam, K Hanada, C Wrzesinski, Z Yu, S Farid, MR Theoret…
The Journal of Immunology, 2004journals.aai.org
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) …
Abstract
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.
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