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,,§
*
Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, 97213;
Department of Biochemistry and Molecular Biology, Oregon Graduate Institute, Portland, OR 97291; and
Oregon Cancer Center and
§
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201
The adoptive transfer of tumor-specific effector T cells can result
in complete regression and cure mice with systemic melanoma, but the
mechanisms responsible for regression are not well characterized.
Perforin- and Fas ligand (APO-1/CD95 ligand)-mediated cytotoxicity have
been proposed as mechanisms for T cell-mediated tumor destruction. To
determine the role of perforin and Fas ligand (FasL) in T cell-mediated
tumor regression in a murine melanoma model, B16BL6-D5 (D5), we
generated D5-specific effector T cells from tumor vaccine-draining
lymph nodes of wild type (wt), perforin knock out (PKO), or FasL mutant
(gld) mice and treated established D5 metastases in mice
with the same genotype. Effector T cells from wt, PKO and
gld mice induced complete regression of pulmonary
metastases and significantly prolonged survival of the treated animals
regardless of their genotype. Complete tumor regression induced by PKO
effector T cells was also observed in a sarcoma model (MCA-310).
Furthermore, adoptive transfer of PKO and wt effector T cells provided
long-term immunity to D5. Therapeutic T cells from wt, PKO, or
gld mice exhibit a tumor-specific type 1 cytokine
profile; they secrete IFN-
, but not IL-4. In these models, T
cell-mediated tumor regression and long-term antitumor immunity are
perforin and FasL independent.
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