Down-modulation of CXCR3 surface expression and function in CD8(+) T cells from cutaneous T cell lymphoma patients

D Winter, J Moser, E Kriehuber, C Wiesner, R Knobler, F Trautinger, P Bombosi, G Stingl, P Petzelbauer, Antal Rot, D Maurer

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4272-4282
Number of pages11
JournalJournal of Immunology
Volume179
Issue number6
Publication statusPublished - 1 Sep 2007

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