title: Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs.
abstract: BACKGROUND
  Myeloid derived suppressor cells (MDSCs) are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines) and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11b low/CADO48 low) cell population that is increased in the peripheral blood of tumor-bearing dogs.
  
  
  RESULTS
  Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11b low/CADO48A low cells (7.9%) as compared to the control dogs (3.6%). Additionally, sorted CD11b low/CADO48A low generated in vitro suppressed the proliferation of canine lymphocytes.
  
  
  CONCLUSIONS
  The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11b low/CADO48A low cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice) and utilizes commercially available canine-specific antibodies. Importantly, CD11b low/CADO48A low from a tumor environment suppress the proliferation of lymphocytes. These results provide a useful phenotype of cells increased in canine cancer patients that may serve as a useful prognostic marker for assessing immune status and functional response to cancer immunotherapies in dogs. Understanding MDSCs in dogs will allow for increased effectiveness of cancer immunotherapy in both dogs and humans.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sherger
authors.forename: William
authors.initials: W
authors.lastname: Kisseberth
authors.forename: Cheryl
authors.initials: C
authors.lastname: London
authors.forename: Susan
authors.initials: S
authors.lastname: Olivo-Marston
authors.forename: Tracey L
authors.initials: TL
authors.lastname: Papenfuss
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D039481:CD11b Antigen / Q000097:blood*; D004283:Dog Diseases / Q000097:blood* / Q000276:immunology / Q000473:pathology; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D016130:Immunophenotyping / Q000662:veterinary; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology*; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D011446:Prospective Studies; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; D039481:CD11b Antigen