Pettinella, F.; Mariotti, B.; Lattanzi, C.; Bruderek, K.; Donini, M.; Costa, S.; Marini, O.; Iannoto, G.; Gasperini, S.; Caveggion, E.; Castellucci, M.; Calzetti, F.; Bianchetto-Aguilera, F.; Gardiman, E.; Giani, M.; Dusi, S.; Cantini, M.; Vassanelli, A.; Pavone, D.; Milella, M.; Pilotto, S.; Biondani, P.; Höing, B.; Schleupner, M. C.; Hussain, T.; Hadaschik, B.; Kaspar, C.; Visco, C.; Tecchio, C.; Koenderman, L.; Bazzoni, F.; Tamassia, N.; Brandau, S.; Cassatella, M. A.; Scapini, P.
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.