Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs

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 modifcying 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.