Abstract
Tumor-specific CD8 T cell responses to MCA102 fibrosarcoma cells expressing the cytotoxic T cell epitope gp33 from lymphocytic choriomeningitis virus were studied. MCA102(gp33) tumors grew progressively in C57BL/6 mice, despite induction of peripheral gp33-tetramer(+) T cells that were capable of mediating antiviral protection, specific cell rejection, and concomitant tumor immunity. MCA102(gp33) tumors were infiltrated with a high number ( approximately 20%) of CD11b(+)CD11c(-) macrophage-phenotype cells that were able to cross-present the gp33 epitope to T cells. Tumor-infiltrating CD8 T cells exhibited a highly activated phenotype but lacked effector cell function. Strikingly, a significant portion of tumor-infiltrating lymphocytes expressed TCRs specific for gp33 but bound MHC tetramers only after cell purification and a 24-h resting period in vitro. The phenomenon of "tetramer-negative T cells" was not restricted to tumor-infiltrating lymphocytes from MCA102(gp33) tumors, but was also observed when Ag-specific T cells derived from an environment with high Ag load were analyzed ex vivo. Thus, using a novel tumor model, allowing us to trace tumor-specific T cells at the single cell level in vivo, we demonstrate that the tumor microenvironment is able to alter the functional activity of T cells infiltrating the tumor mass.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / genetics
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Antigens, Viral / biosynthesis
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Antigens, Viral / immunology
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Antigens, Viral / metabolism*
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CD11b Antigen / biosynthesis
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Division / genetics
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Cell Division / immunology
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Cell Separation
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Cells, Cultured
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Cytotoxicity, Immunologic* / genetics
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Epitopes, T-Lymphocyte / biosynthesis
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Epitopes, T-Lymphocyte / immunology
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Female
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Fibrosarcoma / immunology*
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Fibrosarcoma / metabolism
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Fibrosarcoma / pathology
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Glycoproteins / biosynthesis
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Glycoproteins / immunology
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Glycoproteins / metabolism*
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Histocompatibility Antigens Class I / metabolism*
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Immunity, Innate / genetics
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Lymphocyte Count
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Lymphocytes, Tumor-Infiltrating / immunology*
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Lymphocytes, Tumor-Infiltrating / metabolism*
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Lymphocytes, Tumor-Infiltrating / pathology
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Lymphocytic choriomeningitis virus / immunology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Neoplasm Transplantation
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Peptide Fragments / biosynthesis
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Peptide Fragments / immunology
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Peptide Fragments / metabolism*
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Protein Binding / genetics
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / biosynthesis
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Tumor Cells, Cultured
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Viral Proteins / biosynthesis
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Viral Proteins / immunology
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Viral Proteins / metabolism*
Substances
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Antigens, Viral
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CD11b Antigen
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Epitopes, T-Lymphocyte
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Glycoproteins
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Histocompatibility Antigens Class I
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus