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Blood Myeloid-Derived Suppressor Cells Correlate with Neutrophil-to-Lymphocyte Ratio and Overall Survival in Metastatic Urothelial Carcinoma

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Abstract

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.

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Iris Y. Sheng, Timothy D. Gilligan, Jorge A. Garcia & Moshe C. Ornstein

  2. Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA

    Claudia Marcela Diaz-Montero, Patricia Rayman, James H. Finke, Jin S. Kim & Paul G. Pavicic Jr.

  3. Taussig Cancer Institute, Cleveland, OH, USA

    Wei Wei, Marcelo Lamenza & Donna Company

  4. Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

    Andrew Stephenson, Steven Campbell, George Haber & Byron Lee

  5. Department of Radiation Oncology Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA

    Omar Mian

  6. Division of Hematology Oncology, Vanderbilt University, Nashville, TN, USA

    Brian I. Rini

  7. Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA

    Petros Grivas

  8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Petros Grivas

  9. University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave E. G-4830, Seattle, WA, 98109, USA

    Petros Grivas

  10. Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave, CA-60, Cleveland, OH, 44195, USA

    Moshe C. Ornstein

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  1. Iris Y. Sheng
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Corresponding authors

Correspondence to Petros Grivas or Moshe C. Ornstein.

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Funding

No external funding was used in the preparation of this article.

Conflict of interest

Brian I. Rini declares research funding and consulting for Merck, BMS, Pfizer, Roche, Aveo. Jorge A. Garcia declares consulting for Merck, Janssen, Eisai, Astella, Seattle Genetics and speaking/education for Merck, Janssen and Bayer. Petros Grivas declares prior unrelated consulting for: AstraZeneca; Bayer; Biocept; Bristol-Myers Squibb; Clovis Oncology; Driver; EMD Serono; Exelixis; Foundation Medicine; Genentech; Genzyme; GlaxoSmithKline; Heron Therapeutics; Janssen; Merck & Co.; Mirati Therapeutics; Pfizer; Seattle Genetics; QED Therapeutics; Roche; research funding to institution: AstraZeneca, Bayer; Genentech/Roche; Merck & Co.; Mirati Therapeutics; Oncogenex; Pfizer, Clovis Oncology, Bavarian Nordic, Immunomedics, Debiopharm, Bristol-Myers Squibb. Moshe C. Ornstein declares grant support from Pfizer, BMS; speaking: BMS, Exelixis; education support: Pfizer; consulting: BMS, Pfizer, Exelixis. Iris Y. Sheng, Claudia Marcela Diaz-Montero, Patricia Rayman, Wei Wei, James H. Finke, Jin S. Kim, Paul G Pavicic Jr, Marcelo Lamenza, Donna Company, Andrew Stephenson, Steven Campbell, George Haber, Byron Lee, Omar Mian, and Timothy D. Gilligan declare that they have no conflicts of interest that might be relevant to the contents of this article.

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Sheng, I.Y., Diaz-Montero, C.M., Rayman, P. et al. Blood Myeloid-Derived Suppressor Cells Correlate with Neutrophil-to-Lymphocyte Ratio and Overall Survival in Metastatic Urothelial Carcinoma. Targ Oncol 15, 211–220 (2020). https://doi.org/10.1007/s11523-020-00707-z

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