Human CD34+/dim neutrophil-committed progenitors do not differentiate into neutrophil-like CXCR1+CD14+CD16- monocytes in vitro.

The advent of recent cutting-edge technologies has allowed the discovery and characterization of novel progenitors of human neutrophils, including SSCloCD66b+CD15+CD11b-CD49dhiproNeu1s, SSChiCD66b+CD15+CD11b-CD49dintproNeus2s, CD66b+CD15+CD11b+CD49d+CD101-preNeus, and Lin-CD66b+CD117+CD71+eNePs. In this research field, we recently identified CD66b-CD38+CD64dimCD115-, CD34+, and CD34dim/- cells exclusively committed to the neutrophil lineage (which we renamed as CD34+ and CD34dim/- neutrophil-committed progenitors), representing the earliest neutrophil precursors identifiable and sorted by flow cytometry. Moreover, based on their differential CD34 and CD45RA expression, we could identify 4 populations of neutrophil-committed progenitors: CD34+CD45RA-/NCP1s, CD34+CD45RA+/NCP2s, CD34dim/-CD45RA+/NCP3s, and CD34dim/-CD45RA-/NCP4s. This said, a very recent study by Ikeda and coworkers (PMID: 36862552) reported that neutrophil precursors, termed either neutrophil progenitors or "early neutrophil-committed progenitors," would generate immunosuppressive neutrophil-like CXCR1+CD14+CD16- monocytes. Hence, presuming that neutrophil progenitors/"early neutrophil-committed progenitors" correspond to neutrophil-committed progenitors, the selective neutrophil commitment that we attributed to neutrophil-committed progenitors is contradicted by Ikeda and coworkers' article. In this study, by performing a more analytical reevaluation at the phenotypic and molecular levels of the cells generated by neutrophil-committed progenitors 2 and 4 (selected as representatives of neutrophil-committed progenitors), we categorically exclude that neutrophil-committed progenitors generate neutrophil-like CXCR1+CD14+CD16- monocytes. Rather, we provide substantial evidence indicating that the cells generated by neutrophil progenitors/"early neutrophil-committed progenitors" are neutrophilic cells at a different stage of maturation, displaying moderate levels of CD14, instead of neutrophil-like CXCR1+CD14+CD16- monocytes, as pointed by Ikeda and coworkers. Hence, the conclusion that neutrophil progenitors/"early neutrophil-committed progenitors" aberrantly differentiate into neutrophil-like monocytes derives, in our opinion, from data misinterpretation.

Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors.

Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.