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).
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).
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). 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).
In patients with nonmetastatic UC of bladder, higher WB M-MDSC and UnC-MDSC before cystectomy had negative prognostic value. Prospective validation is warranted.
Clinical genitourinary cancer. 2020 Mar 19 [Epub ahead of print]
Jaleh Fallah, Claudia Marcela Diaz-Montero, Patricia Rayman, Wei Wei, James H Finke, Jin S Kim, Paul G Pavicic, Marcelo Lamenza, Priscilla Dann, Donna Company, Andrew Stephenson, Steven Campbell, George Haber, Byron Lee, Omar Mian, Timothy Gilligan, Jorge A Garcia, Brian Rini, Moshe C Ornstein, Petros Grivas
Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH., Lerner Research Institute, Cleveland Clinic, Cleveland, OH., Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH., Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; Lerner Research Institute, Cleveland Clinic, Cleveland, OH., Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH; Division of Hematology & Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN., Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address: ., Department of Medicine, Division of Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA. Electronic address: .