title: Down-modulation of CXCR3 surface expression and function in CD8+ T cells from cutaneous T cell lymphoma patients.
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.
authors.affiliation: Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Dorian
authors.initials: D
authors.lastname: Winter
authors.forename: Julia
authors.initials: J
authors.lastname: Moser
authors.forename: Ernst
authors.initials: E
authors.lastname: Kriehuber
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiesner
authors.forename: Robert
authors.initials: R
authors.lastname: Knobler
authors.forename: Franz
authors.initials: F
authors.lastname: Trautinger
authors.forename: Paula
authors.initials: P
authors.lastname: Bombosi
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.forename: Antal
authors.initials: A
authors.lastname: Rot
authors.forename: Dieter
authors.initials: D
authors.lastname: Maurer
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D019040:E-Selectin / Q000096:biosynthesis / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D020014:K562 Cells; D019041:L-Selectin / Q000096:biosynthesis; D008024:Ligands; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008247:Lysosomes / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism