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.