Circulating PMN-MDSC level positively correlates with a poor prognosis in patients with metastatic hormone-sensitive prostate cancer

Abstract

Introduction: This study aims to investigated for the first time the role of myeloid-derived suppressor cells (MDSCs) in metastatic-hormone sensitive prostate cancer (mHSPC), which has not been investigated previously. Materials and methods:This was a prospective observational cohort study. MDSC subsets in peripheral blood samples were classified and evaluated by flow cytometry as early-stage MDSCs (e-MDSCs), polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs). The 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 singlecell RNA-sequencing (scRNA-seq) in a representative case.Results: Thirty-one mHSPC patients and 11 healthy controls (HCs) were included in this study. There were significantly more PMN/M-MDSCs in mHSPC patients than in HCs (p <0.05) before treatment, but the numbers became similar to those in HCs after treatment. Although there were no marked differences in the high and low ratios of e-MDSCs and M-MDSCs, patients with a high ratio of PMN-MDSCs (≥0.30%) had a poorer PSA-PFS and OS than those with a low ratio (<0.30%) (p <0.05). scRNA-seq showed that the expression of genes implicated in tumor progression was upregulated in a representative mHSPC case.

Moving toward improved immune checkpoint immunotherapy for advanced prostate cancer

“…As the name implies, MDSCs have immunosuppressive functions and are associated with various pathological conditions, including accumulation in tumors. Peripheral levels of PMN‐MDSCs are elevated in patients with mCRPC and are recruited to tumors where they accumulate 144–146 . Hypoxia, which is a hallmark of cancer and is also prevalent in human CRPC, can also increase levels of extracellular adenosine to recruit myeloid cells into tumors 147–150 .…”

“…Peripheral levels of PMN-MDSCs are elevated in patients with mCRPC and are recruited to tumors where they accumulate. [144][145][146] Hypoxia, which is a hallmark of cancer and is also prevalent in human CRPC, can also increase levels of extracellular adenosine to recruit myeloid cells into tumors. [147][148][149][150] In tumors, PMN-MDSCs produce several suppressive molecules such as IL-23, TGF-b, arginase 1, IL-10, and ROS that dampen effector T-cell function and induce the expansion of Tregs.…”

Increased circulating polymorphonuclear myeloid-derived suppressor cells are associated with prognosis of metastatic castration-resistant prostate cancer

“…Contrarily, the PMN-MDSC levels in prostate cancer patients correlated with advanced cancer stages and predicted poorer outcomes ( 19 ). A recent study on mHSPC patients indicated that PMN-MDSC is a negative prognostic indicator, whereas M-MDSC seemed to have no significant impact ( 20 ). Notably, no detailed studies have examined the background factors associated with MDSC subtype levels by classifying the prostate cancer patients according to hormone sensitivity and metastasis.…”