Abstract
Myeloid-derived suppressor cells (MDSCs) are immature cells with immunosuppressive properties found in the tumor microenvironment. MDSCs are divided into two major subsets: polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Both MDSC subsets contribute to the creation of an immunosuppressive environment for tumor progression. In humans, patients with high levels of MDSCs show worse outcomes for several types of cancers. However, the association between MDSCs and clinical features has rarely been investigated in canine studies. In the present study, we measured the proportion of PMN-MDSCs and M-MDSCs in the peripheral blood and tumor tissue of dogs with hepatocellular carcinoma (HCC), prostate cancer (PC), transitional cell carcinoma (TCC), lymphoma, and pulmonary adenocarcinoma. Additionally, we examined immunosuppressive ability of PMN-MDSCs and M-MDSCs in peripheral blood mononuclear cells of TCC case on CD4+, CD8+ and interferon-γ+ cells and investigated the relationships of MDSCs with clinical features and outcomes. PMN-MDSCs increased in HCC, PC, TCC, and lymphoma. In contrast, M-MDSCs increased in the TCC. Both PMN-MDSCs and M-MDSCs exhibited immunosuppressive effects on CD8+, CD4+ and interferon-γ+ cells. In dogs with TCC, lymph node metastasis was associated with high level of PMN-MDSCs but not with M-MDSCs. High levels of both PMN-MDSCs and M-MDSCs were related to advanced tumor stage. Kaplan-Meier analysis revealed that high levels of both PMN-MDSCs and M-MDSCs were significantly associated with shorter overall survival. In addition, the Cox proportional hazard regression model showed that M-MDSCs and the tumor stage were independent prognostic factors for TCC. These results suggest that PMN-MDSCs and M-MDSCs may be involved in tumor progression and could be prognostic factors and promising therapeutic targets in dogs with TCC.
Published Version
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