Iris Y Sheng1, Claudia Marcela Diaz-Montero2, Patricia Rayman2, Wei Wei3, James H Finke2, Jin S Kim2, Paul G Pavicic2, Marcelo Lamenza3, Donna Company3, Andrew Stephenson4, Steven Campbell4, George Haber4, Byron Lee4, Omar Mian5, Timothy D Gilligan1, Brian I Rini6, Jorge A Garcia1, Petros Grivas7,8,9, Moshe C Ornstein10,11. 1. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. 2. Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA. 3. Taussig Cancer Institute, Cleveland, OH, USA. 4. Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 5. Department of Radiation Oncology Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA. 6. Division of Hematology Oncology, Vanderbilt University, Nashville, TN, USA. 7. Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA. pgrivas@uw.edu. 8. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. pgrivas@uw.edu. 9. University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Ave E. G-4830, Seattle, WA, 98109, USA. pgrivas@uw.edu. 10. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. ornstem@ccf.org. 11. Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave, CA-60, Cleveland, OH, 44195, USA. ornstem@ccf.org.
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.
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.
Authors: Ali Raza Khaki; Ang Li; Leonidas N Diamantopoulos; Natalie J Miller; Lucia Carril-Ajuria; Daniel Castellano; Ivan De Kouchkovsky; Vadim Koshkin; Joseph Park; Ajjai Alva; Mehmet A Bilen; Tyler Stewart; Victor Santos; Neeraj Agarwal; Jayanshu Jain; Yousef Zakharia; Rafael Morales-Barrera; Michael Devitt; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Benjamin A Gartrell; Alex Sankin; Abhishek Tripathi; Roubini Zakopoulou; Aristotelis Bamias; Alejo Rodriguez-Vida; Alexandra Drakaki; Sandy Liu; Vivek Kumar; Mark P Lythgoe; David J Pinato; Jure Murgic; Ana Fröbe; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Pedro Barata; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Veena Shankaran; Gary H Lyman; Petros Grivas Journal: Eur Urol Oncol Date: 2021-01-07
Authors: Ryan Michael Reyes; Yilun Deng; Deyi Zhang; Niannian Ji; Neelam Mukherjee; Karen Wheeler; Harshita B Gupta; Alvaro S Padron; Aravind Kancharla; Chenghao Zhang; Myrna Garcia; Anand V R Kornepati; Onur Boyman; Jose R Conejo-Garcia; Robert S Svatek; Tyler J Curiel Journal: J Immunother Cancer Date: 2021-04 Impact factor: 13.751