Mature PMN-MDSCs from G-CSF-treated healthy donors and cancer patients share a suppressive gene signature and CD84 expression

Recently, we demonstrated that neutrophil populations displaying polymorphonuclear myeloid derived suppressor cell (PMN-MDSC)-like features appear in abundance in both CD66b+ low-density neutrophils (LDNs) and normal-density neutrophils (NDNs) of healthy subjects receiving G-CSF for stem cell mobilization (GDs). We also uncovered that the mature, but not immature, fraction of PMN-MDSC populations present in GDs, similarly to what also shown by others in cancer patients, are those exerting the most potent immunosuppressive functions. Herein, by RNA-seq computational analysis, we report the identification and characterization of a distinct gene signature common to mature CD66b+CD11b+CD16+CD10+ LDNs/mNDNs from GDs (GD-mNDNs/mLDNs) and mature CD66b+CD11b+CD16+CD10+ PMN-MDSCs (mPMN-MDSCs) from head and neck (HNC) and non-small cell lung (NSCLC) cancer patients. We also show that this GD/NSCLC/HNC mPMN-MDSC gene signature derives, mostly from the maintenance of genes already expressed by normal immature neutrophil precursors, and in a minor, but more specific, quote, from genes selectively upregulated along the maturation of PMN-MDSC-committed cells. Furthermore, by searching for mRNAs included within the latter group of genes encoding surface proteins, we found CD84 expression markedly elevated on mPMN-MDSC populations, not only from GDs and HNC/NSCLC, but also from diffuse large B cell lymphoma (DLBCL), renal cell cancer (RCC), transitional cell carcinoma (TCC) and breast cancer (BC) patients. Overall, data prove that mLDNs and mNDNs from GDs represent excellent cellular models suitable either to define the molecular features, or to identify specific markers, that can be shared by mPMN-MDSC populations from different origin.