Exosomal miRNA Cargo as Mediator of Immune Escape Mechanisms in Neuroblastoma

Both natural killer (NK) cells and exosomes released from these cells induce tumor cell cytotoxicity by way of the cell killing proteins perforin and granzyme. TGF beta 1 protein in the tumor microenvironment generates an immune escape mechanism rendering NK cells inactive. The tumor-suppressive miR-186 that is downregulated in neuroblastoma and in TGFb-treated NK cells represses oncogenic proteins in neuroblastoma (MYCN and AURKA) and components of the TGF beta pathway. Restoration of miR-186 levels in neuroblastoma through NK cell-derived exosomes or by nanoparticle delivery reduces tumor burden, promotes survival, and restores the cell-killing abilities of NK cells, demonstrating the therapeutic potential of tumor-suppressive miRNAs in neuroblastoma. See related article by Neviani and colleagues; Cancer Res 79(6): 1151-64