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Erschienen in:
23.03.2020 | Original Research Article
Blood Myeloid-Derived Suppressor Cells Correlate with Neutrophil-to-Lymphocyte Ratio and Overall Survival in Metastatic Urothelial Carcinoma
Erschienen in: Targeted Oncology | Ausgabe 2/2020
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Background
Myeloid-derived suppressor cells (MDSCs) were linked to pathologic stage in bladder urothelial carcinoma (UC). Neutrophil lymphocyte ratio (NLR) is an inflammatory biomarker with a prognostic role in metastatic (m)UC.
Objective
We hypothesized that MDSC levels correlate with NLR and overall survival (OS) in mUC.
Patients and methods
MDSCs were measured in blood samples from patients with mUC in fresh unfractionated whole blood (WB) and peripheral blood mononuclear cells (PBMC) by flow cytometry and defined as LinloCD33+/HLADR- (Total MDSC). MDSC subsets were defined as polymorphonuclear (PMN-MDSC: CD15+/CD14−), monocytic (M-MDSC: CD15−/CD14+), and uncommitted (UNC-MDSC: CD15−/CD14−). MDSC populations were presented as a percentage of live nucleated blood cells. Spearman’s rank correlation assessed correlations between MDSC and NLR. Kaplan–Meier curves and log-rank test estimated OS from the time of MDSC collection to last follow-up or date of death.
Results
Of the 76 patients, 78% were men and 43% were never smokers with a median age of 69 years (range 31–83); 72% had pure UC and 76% had lower tract UC. Prior therapies included intravesical therapy (22%), neoadjuvant chemotherapy (30%), cystectomy or nephroureterectomy (55%). Median follow-up for all patients was 12 months (0.6–36.5). PMN-MDSC was the predominant subset in WB and PBMC. There was significant correlation between individual MDSC subsets in WB and PBMC (p ≤ 0.001). Both WB UNC-MDSC/PMN-MDSC ratios (rho = − 0.27, p = 0.03) and PBMC UNC-MDSC/PMN-MDSC (rho = − 0.28, p = 0.02) were negatively correlated with NLR. Median OS was 17.7 months (95% CI: 11.0–NE). Overall 1-year and 3-year survival rates were 0.60 (95% CI 0.49–0.73) and 0.15 (95% CI 0.03–0.67), respectively. Higher WB UNC-MDSC levels (HR 3.78, p = 0.0022) and higher NLR (HR 2.6, p = 0.0179) were associated with shorter OS.
Conclusions
Specific MDSC subsets correlate with NLR. Higher WB UNC-MDSC levels and higher NLR were negative prognostic factors. Given the feasibility of serial blood draws, dynamic assessment of MDSC over time and further validation with longer follow-up are warranted.
