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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that expand significantly under pathological conditions such as cancer, chronic inflammation, and infection [1, 19]. In the tumor microenvironment (TME), MDSCs play a critical role in promoting tumor progression by potently suppressing anti-tumor immune responses, particularly those mediated by T cells and natural killer (NK) cells [6, 13]. They achieve this through various mechanisms, including the production of immunosuppressive molecules like arginase-1 (ARG1), inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), as well as the secretion of cytokines like IL-10 and TGF-beta [15, 18]. Beyond immune suppression, MDSCs also contribute to tumor angiogenesis, epithelial-mesenchymal transition, and the formation of pre-metastatic niches [16, 25]. Because their presence is strongly associated with poor clinical outcomes and resistance to immune checkpoint inhibitors, MDSCs have emerged as a major therapeutic target [1, 8]. Current pharmacological strategies focus on depleting MDSC populations using low-dose chemotherapy, blocking their recruitment from the bone marrow to the tumor via chemokine receptor antagonists, inhibiting their suppressive metabolic pathways, or inducing their differentiation into mature, non-suppressive myeloid cells [2, 10, 22].
Therapeutic strategies targeting MDSCs include the depletion of existing cell populations, inhibition of their recruitment and trafficking from the bone marrow to the tumor microenvironment, blockade of immunosuppressive effector molecules such as Arginase 1 and iNOS, and the induction of differentiation into mature, non-suppressive myeloid cells.
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