Abstract
A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion protein elicited the formation of a lymphoid-like tissue in the tumor microenvironment containing L-selectin+ T cells and MHC class II+ antigen-presenting cells, as well as B and T cell aggregates. Furthermore, PNAd+/TCA4+ high endothelial venules were observed within the tumor, suggesting entry channels for naive T cell infiltrates. Over the course of therapy, a marked clonal expansion of certain TCR specificities occurred among tumor-infiltrating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruited to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / therapeutic use
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Endothelium, Lymphatic / immunology
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Endothelium, Lymphatic / pathology
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Humans
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Immunotoxins / therapeutic use*
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Lung Neoplasms / immunology
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Lung Neoplasms / secondary
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Lung Neoplasms / therapy
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Lymphocytes, Tumor-Infiltrating / immunology
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Lymphocytes, Tumor-Infiltrating / pathology
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Lymphoid Tissue / immunology
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Lymphoid Tissue / pathology
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Lymphotoxin-alpha / therapeutic use*
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Melanoma, Experimental / immunology*
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Melanoma, Experimental / pathology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred C57BL
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Microscopy, Electron
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Neoplasm Transplantation
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Neoplasms, Connective Tissue / immunology
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Neoplasms, Connective Tissue / pathology
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Neoplasms, Connective Tissue / therapy
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Recombinant Fusion Proteins / therapeutic use
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T-Lymphocytes / immunology
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T-Lymphocytes / pathology
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Transplantation, Isogeneic
Substances
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Antibodies, Monoclonal
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Immunotoxins
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Lymphotoxin-alpha
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Recombinant Fusion Proteins