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

Once diagnosed with metastatic urothelial carcinoma, only very few patients achieve long-term survival with platinum-based chemotherapy. Most patients who respond to initial systemic treatment eventually have tumor progression. With the advent of new treatment strategies such as immune checkpoint and FGFR inhibitors and antibody-drug conjugates, clinical outcomes appear to improve. However, more data is needed for the development of prognostic and predictive biomarkers, as well as novel therapeutic targets.

While clinical prognostic factors such as visceral metastases and poor performance status are associated with shorter survival with systemic chemotherapy, relevant models for patients treated with immune checkpoint inhibitors are being pursued. Prior studies suggested that immune cells, such as myeloid-derived suppressor cells (MDSC), might be associated with response to immune checkpoint inhibitors and outcomes in bladder and other cancers. In our study, we evaluated whether the levels of circulating MDSC and the neutrophil to lymphocyte ratio (NLR) were associated with overall survival (OS) in patients with advanced urothelial cancer treated in a tertiary cancer center.

Our results showed a significant association between MDSC levels measured in whole blood and those measured based on peripheral blood mononuclear cell analysis. Moreover, a higher level of uncommitted MDSC measured in whole blood and higher NLR was associated with shorter OS. The findings do not apply to current clinical practice but support further investigation of MDSC and NLR as putative biomarkers in advanced urothelial cancer in studies with larger sample size and longer follow up.

Written by: Iris Y Sheng, Claudia Marcela Diaz-Montero, Patricia Rayman, Wei Wei, James H Finke, Jin S Kim, Paul G Pavicic, Marcelo Lamenza, Donna Company, Andrew Stephenson, Steven Campbell, George Haber, Byron Lee, Omar Mian, Timothy D Gilligan, Brian I Rini, Jorge A Garcia, Petros Grivas, Moshe C Ornstein

Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA., Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA., Taussig Cancer Institute, Cleveland, OH, USA., Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA., Department of Radiation Oncology Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA., Division of Hematology Oncology, Vanderbilt University, Nashville, TN, USA., Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA., Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.

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