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

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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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Acknowledgments

The authors would like to thank all patients who participated in the study, and Hillevi Björkqvist and Ann-Louise Helminnen for valuable help with collection of clinical samples. We also thank the Centre of Cellular Imaging (CCI) at the Sahlgrenska Academy for providing microscope training and equipment. The study was supported by grants from the Swedish Research Council, the Swedish Cancer Foundation, the Sahlgrenska University Hospital, Assar Gabrielssons foundation, Inga Britt and Arne Lundgren’s foundation and Professor Nanna Svartz’s Foundation.

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The authors declare that they have no conflict of interest.

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Correspondence to Veronica Langenes.

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Veronica Langenes and Helena Svensson have contributed equally.

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Langenes, V., Svensson, H., Börjesson, L. et al. Expression of the chemokine decoy receptor D6 is decreased in colon adenocarcinomas. Cancer Immunol Immunother 62, 1687–1695 (2013). https://doi.org/10.1007/s00262-013-1472-0

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