Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated With Pathologic Complete Response and Overall Survival |
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| Affiliation: | 1. Department of Urology, The No.1 Hospital of Shijiazhuang/Shijiazhuang People''s Hospital, Shijiazhuang, China;2. Institute of Medicine and Health, Hebei Medical University, Shijiazhuang, China;1. CEDECOR (Centro de Estudio de Compuestos Orgánicos), Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), Calle 115 y 47, 1900 La Plata, Argentina;2. CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Argentina;3. Instituto de Física del Sur (IFISUR), Departamento de Física, Universidad Nacional del Sur (UNS), CONICET, Av. L.N. Alem 1253, B8000CPB Bahía Blanca, Argentina;4. Universidad Tecnológica Nacional (UTN), 11 de Abril 461, B8000LMI Bahía Blanca, Argentina;5. Grupo de Catálisis y Procesos de Separación (CyPS), Departamento de Ingeniería Química y de Materiales, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040 Madrid, Spain;6. Comisión de Investigaciones Científicas (CIC), Calle 526 e/10 y 11, 1900 La Plata, Argentina. |
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| Abstract: | ![]()
BackgroundMyeloid-derived suppressor cells (MDSC) have immunosuppressive activity and enhance tumor progression. We hypothesized that lower blood MDSC would correlate with pathologic complete response and better outcomes in nonmetastatic urothelial carcinoma (UC).Patients and MethodsBefore cystectomy, blood MDSC were measured in whole blood (WB) and peripheral blood mononuclear cells using flow cytometry. MDSC were defined as CD33+/HLA-DR−. MDSC subtypes were polymorphonuclear MDSC (CD15+/CD14−), monocytic (M)-MDSC (CD15−/CD14+), and uncommitted (UnC) MDSC (CD15−/CD14−). The Wilcoxon rank sum test was used to compare MDSC between pathologic complete response groups. The optimal cutoff points for MDSC were identified using recursive partitioning analysis with cross-validation. The Cox proportional hazard model was used to associate MDSC and other clinical factors with recurrence-free survival and overall survival (OS).ResultsOverall, 109 patients were included: 86% men with median (range) age of 67 (30-88) years, 76% with pure UC, 29% intravesical therapy, and 41% neoadjuvant chemotherapy. Twenty-one patients (19%) had pT0N0 and 23 (24%) < pT2N0. Median (range) follow-up time was 17.4 (0.4-42.4) months. Total MDSC and polymorphonuclear MDSC percentage in peripheral blood mononuclear cells was significantly lower in patients with pT0N0 disease (P = .03). One- and 2-year OS rates were 94% (95% confidence interval [CI], 90-99) and 83% (95% CI, 75-93), respectively. In the multivariate Cox model after adjusting for age and gender, patients with higher WB M-MDSC and UnC-MDSC had shorter OS (optimal cutoff points by recursive partitioning analysis, hazard ratio = 7.5 [95% CI, 2.5-22.8], P = .0004; hazard ratio = 3.4 [95% CI, 1.0-11.0], P = .046, respectively).ConclusionIn patients with nonmetastatic UC of bladder, higher WB M-MDSC and UnC-MDSC before cystectomy had negative prognostic value. Prospective validation is warranted. |
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| Keywords: | Biomarkers Bladder cancer Cystectomy Immune system Immunosuppression |
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