Journal
APMIS
Volume 131, Issue 8, Pages 381-393Publisher
WILEY
DOI: 10.1111/apm.13306
Keywords
Exosome; macrophage polarization; multiple myeloma
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It has long been speculated that leukemic cells can influence resident cells in the tumor microenvironment to promote tumor development. Exosomes, specifically those derived from multiple myeloma cells, have been shown to affect the polarization of macrophages towards M2-like cells. This leads to changes in gene expression, immunophenotyping markers, cytokine secretion, and intracellular signaling in macrophages.
It has long been hypothesized that leukemic cells are able to modulate the fate of resident cells in the tumor microenvironment (TME) toward either supporting or immunosuppressive cells for the development of tumors. Exosomes can be a potential culprit in imposing tumor desire. There is evidence about the impact of tumor-derived exosomes 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 exosomes on the polarization of macrophages by examining hallmarks of M1 and M2 macrophages. After treatment of M0 macrophages with isolated exosomes (from U266B1), gene expression (Arg-1, IL-10, TNF-alpha and IL-6), immunophenotyping markers (CD206), cytokine secretion (IL-10 and IL-6), nitric oxide (NO) production, and redox potentiality of target cells were assessed. Our results revealed significantly increased expression of the genes involved in the development of M2-like cells but not M1 cells. The CD 206 marker and IL-10 protein levels were significantly increased at 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 NO production and intracellular ROS levels in M0 cells.
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