Alpha-melanocyte-stimulating hormone and its impact on myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSCs) are key mediators of tumor-associated immune suppression. Alpha-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with immunomodulatory properties that has been shown to reduce MDSC expansion in a murine carcinogenesis model. However, its molecular effects on human MDSC differentiation remain poorly understood. Here, we investigated the transcriptional effects of α-MSH during GM-CSF and IL-6 induced differentiation of T and B cell depleted, myeloid enriched peripheral blood cells from healthy donors. Whole transcriptome analysis revealed gene expression changes during cytokine induced differentiation and subtle but reproducible transcriptional alterations following α-MSH treatment. Differentially expressed genes were mainly associated with immune regulation, intracellular signaling, cell migration and metabolic processes. These data provide insight into the molecular mechanisms underlying α-MSH-mediated regulation of human MDSC differentiation and serve as a resource for future studies of melanocortin signaling in human myeloid cells.