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Expression of the chemokine decoy receptor D6 is decreased in colon adenocarcinomas.

Journal article
Authors Veronica Langenes
Helena Svensson
Lars Börjesson
Bengt Gustavsson
Mats Bemark
Åsa Sjöling
Marianne Quiding-Järbrink
Published in Cancer immunology, immunotherapy : CII
Volume 62
Issue 11
Pages 1687-1695
ISSN 1432-0851
Publication year 2013
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine, Department of Microbiology and Immunology
Pages 1687-1695
Language en
Links dx.doi.org/10.1007/s00262-013-1472-...
Subject categories Cancer and Oncology, Surgery, Tumour immunology

Abstract

Recruitment of immune cells to tumors is a complex process crucial for both inflammation-driven tumor progression and specific anti-tumor cytotoxicity. Chemokines control the directed migration of immune cells, and their actions are partly controlled by nonsignaling chemokine decoy receptors. The role of the receptors such as D6, Duffy antigen receptor for chemokines and ChemoCentryx chemokine receptor in immunity to tumors is still unclear. Using real-time PCR, we detected significantly decreased expression of D6 mRNA in colon tumors compared to unaffected mucosa. D6 protein was expressed by lymphatic endothelium and mononuclear cells in the colon lamina propria and detected by immunohistochemistry in two out of six tissue samples containing high D6 mRNA levels, whereas no staining was observed in any tissue samples expressing low mRNA levels. When examining the density of lymphatic vessels in colon tumors, we detected a marked increase in vessels identified by the lymphatic endothelial marker Lyve-1, excluding passive regulation of D6 due to decreased lymphatic vessel density. In parallel, the Treg-recruiting chemokine CCL22, which is sequestered by D6, was threefold increased in tumor tissue. Furthermore, we could show that low D6 expression correlated to more invasive tumors and that tumor location influences D6 expression, which is lower in the more distal parts of the colon. The data support that regulation of D6 by colon tumors results in altered levels of proinflammatory CC chemokines, thereby shaping the local chemokine network to favor tumor survival. This may have implications for the design of future immunotherapy for colon cancer.

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