High CD163+CD206+ macrophage infiltration in the bone marrow microenvironment of newly diagnosed multiple myeloma patients.

Abstract

Multiple myeloma (MM) is a neoplastic disease caused by abnormal clonal plasma cells in the bone marrow (BM). Macrophages (MФs) are essential components of BM microenvironment and crucial mediators of plasma cells. Therefore, investigating alterations in the specific MФ subsets within the MM BM microenvironment is of significant importance for elucidating the underlying mechanisms of MM. Here, using flow cytometry, we characterized the dynamics of BM MФ subsets in newly diagnosed multiple myeloma (NDMM) patients and complete remission multiple myeloma (CRMM) patients. We found that NDMM patients exhibited increased infiltration of CD163+CD206+ MФs and elevated levels of interleukin (IL)-6 and IL-10 in the BM compared with CRMM patients and healthy control subjects. BM intermediate monocytes and nonclassical monocytes were increased in NDMM patients compared with those in CRMM patients and healthy control subjects. Furthermore, we observed upregulated CCR2 and CSF-R expression on the BM CD163+CD206+ MФs. Notably, the BM CD163+CD206+CCR2+ MФs were positively correlated with the increased level of IL-6, while CD163+CD206+CSF-R+ MФs were positively correlated with the level of IL-10. Additionally, clinical correlation analysis revealed that an increased proportion of CD163+CD206+CCR2+ MФs was negatively correlated with hemoglobin levels and positively correlated with β2-microglobulin and lactate dehydrogenase. Moreover, a higher proportion of CD163+CD206+CCR2+ MФs was detected in the BM of MM patients with poor prognosis. Altogether, our findings suggest that higher proportion of BM CD163+CD206+ MФs is involved in pathogenesis of MM, and that CCR2 may be potential therapeutic targets for improving antitumor therapy in MM.