Abstract
Viruses can escape destruction by the immune system by exploitation of the chemokine-chemokine receptor system. It is less established whether human cancers can adopt similar strategies to evade immunologic control. In this study, we show that advanced cutaneous T cell lymphoma (CTCL) is associated with selective and efficient inactivation of CXCR3-dependent T cell migration. Our studies demonstrate that this alteration is at least in part due to CXCR3 down-regulation in vivo by elevated serum levels of CXCR3 ligands. The T cell population most affected by this down-regulatory mechanism are CD8+ cytotoxic effector T cells. In CTCL patients, cytotoxic effector T cells have strongly reduced surface CXCR3 expression, accumulate in peripheral blood, but are virtually absent from CTCL tumor lesions, indicating an inability to extravasate into lymphoma tissue. CTCL-associated inactivation of effector cell recruitment may be a paradigmatic example of a new type of immune escape mechanisms shielding the neoplasm from a tumoricidal attack.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / pathology
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Cell Membrane
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Cell Movement / immunology
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Cells, Cultured
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Down-Regulation / immunology*
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E-Selectin / biosynthesis
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E-Selectin / metabolism
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Endosomes / metabolism
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Endothelial Cells / metabolism
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Humans
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Immunologic Memory
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K562 Cells
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L-Selectin / biosynthesis
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Ligands
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Lymphoma, T-Cell, Cutaneous / immunology*
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Lymphoma, T-Cell, Cutaneous / metabolism
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Lymphoma, T-Cell, Cutaneous / pathology
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Lymphoma, T-Cell, Cutaneous / therapy
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Lysosomes / metabolism
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Receptors, CXCR3
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Receptors, Chemokine / antagonists & inhibitors*
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / physiology
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Resting Phase, Cell Cycle / immunology
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Skin Neoplasms / immunology*
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Skin Neoplasms / therapy
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Tumor Cells, Cultured
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Vascular Cell Adhesion Molecule-1 / biosynthesis
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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CXCR3 protein, human
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E-Selectin
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Ligands
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Receptors, CXCR3
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Receptors, Chemokine
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Vascular Cell Adhesion Molecule-1
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L-Selectin