Identification of myeloid-derived suppressor cells in dogs (170.2)

Abstract

Abstract Approximately six million dogs are diagnosed with cancer each year in the United States.Naturally occurring malignances in dogs share many features with human cancers that make dogs an excellent outbred spontaneous tumor model. The accumulation of myeloid derived suppressor cells (MDSCs) in tumor-bearing mice and in humans with cancer is known to be a key mechanism of tumor escape from immune surveillance and antitumor immunity. Due to their remarkable ability to downregulate the immune response against cancer cells in mice and in humans, we hypothesized that MDSCs would also play important role in tumor-induced immune suppression in dogs with cancer. Peripheral blood mononuclear cells of dogs with a variety of cancers and of age-matched healthy control dogs were analyzed by flow cytometry. Immunophenotyping revealed that dogs with cancer exhibited a significantly higher percentage of CD11b+ CD14- MHCII- cells compared with healthy dogs. More importantly, these cells have polymorphonuclear granulocyte morphology and demonstrated an ability to suppress T-cell proliferation in a dose dependent manner. Therefore, according to these results, canine MDSCs do exist and can be a potential target for therapeutic interventions in dogs with cancer. Furthermore, the study of MDSCs in dogs can be used to address underlying questions of resistance and evasion of malignant tumors that comprise an important target for translation cancer immunotherapy.