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Multiple myeloma cell-derived exosomes promote tumor favorable functional performance by polarization of macrophages toward M2 like cells.

It has long been hypothesized that leukemic cells are able to modulate the fate of resident cells in tumoral microenvironment toward a supporting and immunosuppressive cell for development of tumor. Exosome can be a potential culprit in imposing tumor desire. There are evidences about impact of tumor-derived exosome on different immune cells in different malignancies. However, findings about macrophages are contradictory. Here, we evaluated the potential influence of Multiple myeloma (MM)-cell derived exosome on polarization of macrophages by examining hallmarks for M1 and M2 macrophages. After treatment of M0 macrophages with isolated exosomes (from U266B1), gene expression (Arg-1, IL-10, TNF-α and IL-6), immunophenotyping markers (CD206), cytokine secretion (IL-10 and IL-6), nitric oxide (NO) production, and redox potentiality of target cell were assessed. Our results revealed significantly increased expression of the genes involved in development of M2 like cells but not M1 cells. CD 206 marker and IL-10 protein level (specific for M2 like cells) were significantly increased in different time points. The expression of IL-6 mRNA and IL-6 protein secretion did not change significantly. MM-cell derived exosomes induced significant changes in the NO production and intracellular ROS levels in M0 cells.

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