Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate under pathological conditions such as cancer, where they contribute to immune evasion, tumor progression, and resistance to therapy. These cells exert potent immunosuppressive effects by inhibiting T cell activation, inducing regulatory T cells, modulating antigen-presenting cells, and shaping an immunosuppressive tumor microenvironment (TME). Their suppressive functions involve multiple mechanisms, including amino acid depletion, production of reactive oxygen and nitrogen species, expression of immune checkpoint ligands, and secretion of immunoregulatory cytokines such as IL-10 and TGF-β. Besides these immune-related roles, MDSCs also promote tumor growth through non-immunological mechanisms, including the stimulation of angiogenesis and undergoing metabolic reprogramming. These adaptations support their survival and function in the hostile TME. Given their multifaceted role in cancer, MDSCs represent a promising target for therapeutic intervention. Furthermore, their abundance and dynamic modulation during treatment confer them tremendous potential as biomarkers to monitor therapy efficacy and stratify patients. This review provides a comprehensive overview of MDSC biology, their mechanisms of action, and their emerging clinical relevance as biomarkers and therapeutic targets. We also explore current strategies aimed at targeting MDSCs, including their depletion, inhibition of recruitment, functional blockade, and promotion of their differentiation into mature myeloid cells. Integrating these approaches with existing cancer therapies holds great promise for enhancing antitumor immunity and overcoming resistance in both solid tumors and hematologic malignancies.
Keywords: immune biomarkers; immunotherapy; myeloid-derived suppressor cells; tumor microenvironment.
© 2025 Silva-Romeiro et al.