title: Immunosuppressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients.
abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice. We compared the frequency and function of MDSC subsets in dissociated human spleen from 16 patients with benign pancreatic cysts and 26 patients with a variety of cancers. We found that total MDSCs (LinnegCD11bposCD33posHLA-DRneg), granulocytic MDSCs (additional markers CD14negCD15pos), and monocytic MDSCs (CD14posCD15neg) were identified in human spleen. The monocytic subset was the most prominent in both spleen and peripheral blood and the granulocytic subset was expanded in the spleen relative to matched peripheral blood samples. Importantly, the frequency of CD15posMDSCs in the spleen was increased in patients with cancer compared to patients with benign pancreatic cysts and was associated with a significantly increased risk of death and decreased overall survival. Finally, MDSCs isolated from the spleen suppressed T cell responses, demonstrating for the first time the functional capacity of human splenic MDSCs. These data suggest that the human spleen is a potential source of large quantities of cells with immunosuppressive function for future characterization and in-depth studies of human MDSCs.
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, 12631 E. 17th Ave, Aurora, CO, 80045, USA.|Division of Medical Oncology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.|Young Women's Breast Cancer Translational Program, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Kimberly R
authors.identifier: http://orcid.org/0000-0001-8380-7157
authors.initials: KR
authors.lastname: Jordan
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, 12631 E. 17th Ave, Aurora, CO, 80045, USA.
authors.forename: Puja
authors.initials: P
authors.lastname: Kapoor
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, 12631 E. 17th Ave, Aurora, CO, 80045, USA.|University of Colorado Hospital, Aurora, CO, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Spongberg
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, 12631 E. 17th Ave, Aurora, CO, 80045, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Tobin
authors.affiliation: Department of Pediatrics, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Gao
authors.affiliation: Division of Medical Oncology, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.|Young Women's Breast Cancer Translational Program, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.|University of Colorado Cancer Center, Aurora, CO, USA.
authors.forename: Virginia F
authors.initials: VF
authors.lastname: Borges
authors.affiliation: Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, 12631 E. 17th Ave, Aurora, CO, 80045, USA. martin.mccarter@ucdenver.edu.|University of Colorado Cancer Center, Aurora, CO, USA. martin.mccarter@ucdenver.edu.
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCarter
mesh_terms: D000328:Adult; D000368:Aged; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality; D010181:Pancreatic Cyst / Q000276:immunology*; D013154:Spleen / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape
keywords: Cancer; Human spleen; Immunosuppression; MDSCs