<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma"^^ . "Melanoma progression and immunosuppression in the melanoma microenvironment are significantly fueled by myeloid-derived suppressor cells (MDSCs). MDSC generation in melanoma is mediated by several mediators, including soluble and extracellular vesicles (EV)-associated factors. This study aims to investigate the molecular mechanisms initiated in myeloid cells by melanoma EV-associated microRNA (miR), leading to their conversion to MDSCs, as well as the function of endosomal Toll-like receptors (TLR) in these mechanisms. Using synthetic mimics of miR previously described to be enriched in melanoma EVs, I examined their effects on immature myeloid cells (iMCs) isolated from healthy wild-type mice or TLR-deficient mice. Programmed cell death 1 ligand 1 (PD-L1) was utilized as a marker to identify a MDSC-like phenotype, as it has been shown to be a key immunosuppressive molecule in EV-induced MDSCs. To investigate the involvement of signaling pathways in the regulation of MDSC functions, inhibitors of NF-κB activation or Stat3 activation were utilized. Moreover, I studied the influence of miR mimics on human monocytes isolated from the peripheral blood of healthy donors. \r\nTransfection of iMCs with miR mimics of miR-125a-5p, -125b-5p, or -99b-5p induced the expression of PD-L1 on these cells. A positive correlation was observed between miR 125a-5p levels in the tumor microenvironment (TME) and the tumor progression in the RET transgenic mouse model. Furthermore, mimics of miR-125a-5p and the miR cluster 99b/let-7e/125a mediated the upregulation of several MDSC-related factors in iMCs, including IL-6 and reactive oxygen species (ROS). The regulation of PD-L1 expression in iMCs by miR-125a-5p or the miR cluster 99b/let-7e/125a required NF κB activation, however, it was independent of endosomal TLRs and of STAT3 activation. Similarly, human monocytes did not show clear evidence of STAT3 activation by mimics of miR-125a-5p or the miR cluster 99b/let-7e/125a. Nevertheless, mimics of miR-125a-5p or the miR cluster 99b/let-7e/125a mediated the upregulation of PD-L1 in human monocytes. Additionally, a strong trend of the miR cluster 99b/let-7e/125a to downregulate MHC class II and costimulatory CD86 molecules in human monocytes was observed. Furthermore, human monocytes treated with mimics of the miR cluster 99b/let-7e/125a were able to inhibit proliferation of activated T cells. The finding that miR-125a-5p and the three miRs of the cluster 99b/let-7e/125a showed comparable effects on myeloid cells led to the conclusion that mainly melanoma EV-associated miR-125a-5p could contribute to MDSC generation via NF-κB activation."^^ . "2024" . . . . . . . "Samantha"^^ . "Lasser"^^ . "Samantha Lasser"^^ . . . . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (PDF)"^^ . . . "DissertationLasser.pdf"^^ . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (Other)"^^ . . . . . . "preview.jpg"^^ . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (Other)"^^ . . . . . . "medium.jpg"^^ . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (Other)"^^ . . . . . . "small.jpg"^^ . . . "MDSC activation mediated by extracellular vesicles-associated microRNA in melanoma (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #35038 \n\nMDSC activation mediated by extracellular vesicles-associated microRNA in melanoma\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .