Myeloid-derived suppressor cells (MDSCs) play a complex role in cancer progression, influencing immune responses, tumor growth, and metastasis. These cells, which are immature myeloid cells with immunosuppressive properties, are distinct from mature myeloid cells like macrophages and neutrophils. MDSCs can be divided into two main subsets: M-MDSCs (mononuclear) and PMN-MDSCs (polymorphonuclear), distinguished by markers such as Ly6C and Ly6G. In humans, MDSCs are identified in the mononuclear fraction, with PMN-MDSCs being CD14-CD11b+CD33+CD15+ or CD66b+ cells, and M-MDSCs being CD14+HLA-DR-/lo cells. The role of MDSCs in cancer is multifaceted, including immune suppression, tumor microenvironment remodeling, premetastatic niche formation, and promotion of tumor stemness and epithelial-mesenchymal transition (EMT). MDSCs can be targeted for therapeutic purposes, either by eliminating them, deactivating their suppressive functions, or skewing myelopoiesis away from MDSC accumulation. Therapeutic strategies include chemotherapy, targeting suppressive machinery (e.g., PDE-5 inhibitors, NO-releasing aspirin), and modulating myelopoiesis (e.g., ATRA, sunitinib). MDSCs also serve as biomarkers for tumor progression and response to therapy, with their levels correlating with poor clinical outcomes. Understanding MDSC biology is crucial for developing effective cancer therapies.Myeloid-derived suppressor cells (MDSCs) play a complex role in cancer progression, influencing immune responses, tumor growth, and metastasis. These cells, which are immature myeloid cells with immunosuppressive properties, are distinct from mature myeloid cells like macrophages and neutrophils. MDSCs can be divided into two main subsets: M-MDSCs (mononuclear) and PMN-MDSCs (polymorphonuclear), distinguished by markers such as Ly6C and Ly6G. In humans, MDSCs are identified in the mononuclear fraction, with PMN-MDSCs being CD14-CD11b+CD33+CD15+ or CD66b+ cells, and M-MDSCs being CD14+HLA-DR-/lo cells. The role of MDSCs in cancer is multifaceted, including immune suppression, tumor microenvironment remodeling, premetastatic niche formation, and promotion of tumor stemness and epithelial-mesenchymal transition (EMT). MDSCs can be targeted for therapeutic purposes, either by eliminating them, deactivating their suppressive functions, or skewing myelopoiesis away from MDSC accumulation. Therapeutic strategies include chemotherapy, targeting suppressive machinery (e.g., PDE-5 inhibitors, NO-releasing aspirin), and modulating myelopoiesis (e.g., ATRA, sunitinib). MDSCs also serve as biomarkers for tumor progression and response to therapy, with their levels correlating with poor clinical outcomes. Understanding MDSC biology is crucial for developing effective cancer therapies.