Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors
Francesca PettinellaBarbara MariottiChiara LattanziKirsten BruderekMarta DoniniSara CostaOlivia MariniGiulia IannotoSara GasperiniElena CaveggionMonica CastellucciFederica CalzettiFrancisco M. Bianchetto-AguileraElisa GardimanM. GianiStefano DusiMaurizio CantiniAurora VassanelliDenise PavoneMichèle MilellaSara PilottoPamela BiondaniBenedikt HöingMarie Carolin SchleupnerTimon HussainBoris HadaschikCordelia KasparCarlo ViscoCristina TecchioLeo KoendermanFlavia BazzoniNicola TamassiaSven BrandauMarco A. CassatellaPatrizia Scapini
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Abstract:
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.Keywords:
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