The novel biomarker of alternative macrophage activation, soluble mannose receptor (sMR/sCD206): Implications in multiple myeloma

Tumor-associated macrophages (TAMs) play an important role in the pathophysiology of human malignancies. They support growth of cancer cells by promoting angiogenesis, and by inhibiting tumour cell apoptosis and anti-tumor immune reactions. Several membrane proteins are well-described markers of human TAMs, including the haemoglobin scavenger receptor CD163 and the macrophage mannose receptor (MR/CD206). Interestingly, both CD163 and MR exist as soluble serum proteins (sCD163 and sMR) that may reflect the activation state of tissue macrophages, including TAMs. Here, we report the first data on sMR as a biomarker in patients with a malignant disease. We have measured concentrations of sMR in peripheral blood serum (n=104) from patients with newly diagnosed multiple myeloma (MM) by an enzyme-linked immunosorbent assay, and examined associations with data from medical records. At diagnosis, sMR levels were elevated in 27% of patients, and decreased after treatment. Further, sMR levels were associated with prognostic markers in MM, and elevated sMR (>0.43mg/L) was an independent marker of overall survival in a multivariate analysis (HR=2.20, P=0.006). Levels of sMR in blood samples showed significant association with sCD163, which may indicate common origin from CD163+MR+TAMs.