P006 | The IL8-CXCR1/CXCR2 axis plays a role in the mobilization process of polymorphonuclear myeloid-derived suppressor cells in patients with primary myelofibrosis

Introduction. PMF is a myeloproliferative neoplasm characterized by a chronic inflammatory state that contributes to the disease pathogenesis. MDSCs are immature myeloid cells that expand in patients with cancer, sepsis or chronic inflammation favoring tumor onset and progression mainly through the decrease in immune surveillance and the promotion of neoangiogenesis. We previously found that the PMN-MDSC subset is increased both in the circulation and in the spleen of PMF patients and strongly correlates with disease progression (Campanelli R, 2024). Although the precise mechanism underlying the egress of MDSCs from the bone marrow (BM) is unknown, some papers suggest that migration of neutrophils and MDSCs is due to CXC chemokines and inflammatory cytokines. Aim of the study is to investigate the role of IL8 and its receptors (CXCR1, CXCR2) in the mobilization of PMN-MDSCs in PMF.Methods. PMN-MDSCs were identified, sorted by FACS and sequenced by Illumina using the Stranded Total RNA Prep, Ligation with Ribo-Zero Plus Kit. We analysed PMF patients (n=8) and G-CSF-mobilized healthy subjects (G-HDs; n=7). We also measured the membrane expression of CXCR1/2 on PMN-MDSC as percentage and mean fluorescence intensity (MFI) (see Figure). Results. In PMN-MDSCs, the gene expression analysis, expressed as FKPM, showed that IL8 was highly expressed (p