A core of differentially methylated CpG loci in gMDSCs isolated from neonatal and adult sources

Abstract

Background: Myeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype. Results: Using the Illumina EPIC array to measure DNAm of gMDSCs and neutrophils from diverse neonatal and adult blood sources, we found 189 differentially methylated CpGs between gMDSCs and neutrophils with a core of ten differentially methylated CpGs that were consistent across both sources of cells. Genes associated with these loci that are involved in immune responses include VCL, FATS, YAP1, KREMEN2, UBTF, MCC-1, and EFCC1. In two cancer patient groups that reflected those used to develop the methylation markers (head and neck squamous cell carcinoma (HNSCC) and glioma), all of the CpG loci were differentially methylated, reaching statistical significance in glioma cases and controls, while one was significantly different in the smaller HNSCC group. Conclusions: Our findings indicate that gMDSCs have a core of distinct DNAm alterations, informing future research on gMDSC differentiation and function.