Correlation between high ratio of circulating PMN-MDSCs and poor prognosis in metastatic hormone sensitive prostate cancer

Abstract Introduction: This study aims to investigate the role of myeloid-derived suppressor cells (MDSCs) in metastatic-hormone sensitive prostate cancer (mHSPC).Materials and methods: MDSC subsets in peripheral blood samples were classified and evaluated by flow cytometry into early MDSCs (e-MDSCs), polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs). Prostate-specific antigen progression free survival (PSA–PFS) and overall survival (OS) were evaluated to assess the prognostic value of each of the MDSC subsets. The immune cell dynamics and gene expression alteration were analyzed by single cell RNA sequencing (scRNA-seq) in the representative case.Results: Thirty-one patients with mHSPC and eleven healthy controls (HCs) were included in this study. In patients with mHSPC, PMN/M-MDSCs were significantly higher than those of HCs (p < 0.05) before treatment and declined to almost the same level as in the HCs after treatment. Although there were no differences between high and low ratio of e-MDSCs and M-MDSCs, patients with a high ratio of PMN-MDSCs (≥ 0.30%) displayed a lower PSA–PFS and OS than those with a low ratio (< 0.30%) (p < 0.05). The analysis of scRNA-seq showed that the expression of genes implicated in tumor progression was upregulated in a representative mHSPC case.Conclusion: The high frequency of PMN-MDSCs correlated with poor prognosis in patients with mHSPC. PMN-MDSCs and their highly expressed genes are included as potential novel therapeutic targets for mHSPC.