Circulating extracellular vesicle-associated CD163 and CD206 in multiple myeloma.

Abstract

Extracellular vesicles (EVs) are important for intercellular signalling in cancer. Tumour-associated macrophages, expressing the haemoglobin-haptoglobin and mannose receptors CD163 and CD206, are crucial for cancer progression. We recently identified CD163 on EVs in the circulation as a fraction of total soluble CD163 (sCD163). Here, we investigated the presence of CD163 and CD206-positive EVs (EV-CD163, EV-CD206) in patients with multiple myeloma (MM). We enrolled patients with MM (n=32), monoclonal gammopathy of undetermined significance (MGUS) (n=8) and healthy donors (n=16). Plasma protein levels were determined by ELISA before and after vesicle precipitation. Monocytes were examined by flow cytometry, and leucocyte CD163 mRNA by qPCR. Fractions of EV-CD163 and EV-CD206 were significantly elevated in patients with newly diagnosed MM (median=39.8%, 76.5%, respectively) compared to patients with relapse (15.6%, P=.02, 42.5%, P=.003), remission (16.9%, P<.0001, 25.2%, P<.0001), MGUS (17.8%, P<.01, 33.1%, P=.0005) and healthy donors (14.8%, P<.0001, 35.5%, P<.0001). Whole blood CD163 mRNA did not vary between the groups. The intermediate monocyte subset showed a higher CD163 expression in newly diagnosed patients. Our results indicate that macrophage-derived EVs may play a role in the late phase of malignant progression of MM, and encourage further EV investigations in functional experiments.