Several experimental approaches have shown that a variety of chemokines have anti-tumour activity either by chemoattracting natural killer cells, monocytes and macrophages, or by accumulating dendritic cells.¹ Accumulating evidence has shown that fractalkine (CX3CL1), the unique member of the CX3C chemokine subfamily, is involved in the pathogenesis of different types of cancer^2,3 and in various clinical disease states beyond cancer, such as atherosclerosis, glomerulonephritis, rheumatoid arthritis, HIV disease and sepsis.^4–6 In contrast with other chemokines, fractalkine exists in two forms, each mediating distinct biological actions.⁷ The membrane-anchored protein, which is expressed primarily on the endothelium, serves as an adhesion protein promoting the retention of monocytes and T cells.⁸ The soluble form originates from extracellular proteolysis by proteases, such as tumour necrosis factor-α converting enzyme (also known as ADAM17) and ADAM10.⁹ The secreted form resembles more a conventional chemokine and strongly induces chemotaxis and causes migration of natural killer cells, cytotoxic T lymphocytes and macrophages. Both chemotaxis and adhesion are mediated by the G protein-coupled receptor CX3CR1,¹⁰ which is present on natural killer cells, CD14+ monocytes and on some subpopulations of T cells.

In a variety of pathological conditions, fractalkine …