Down-modulation of CXCR3 surface expression and function in CD8+ T cells from cutaneous T cell lymphoma patients |
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Authors: | Winter Dorian Moser Julia Kriehuber Ernst Wiesner Christoph Knobler Robert Trautinger Franz Bombosi Paula Stingl Georg Petzelbauer Peter Rot Antal Maurer Dieter |
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Institution: | Research Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria. |
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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. |
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