Journal
CLINICAL GENITOURINARY CANCER
Volume 18, Issue 6, Pages 500-508Publisher
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clgc.2020.03.004
Keywords
Biomarkers; Bladder cancer; Cystectomy; Immune system; Immunosuppression
Categories
Funding
- NCI NIH HHS [L30 CA220908] Funding Source: Medline
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Myeloid-derived suppressor cells (MDSC) enhance tumor progression. In this study, MDSC level in peripheral blood of 109 patients with nonmetastatic urothelial carcinoma of bladder was measured before cystectomy, and the associations with treatment response and outcomes were investigated. Higher MDSC level in blood was associated with poor response to treatment and worse survival. Background: Myeloid-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 Methods: Before 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). Results: Overall, 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). Oneand 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). Conclusion: In patients with non metastatic UC of bladder, higher WB M-MDSC and UnC-MDSC before cystectomy had negative prognostic value. Prospective validation is warranted. (C) 2020 Elsevier Inc. All rights reserved.
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