Noncoding RNA-Mediated Regulation of Myeloid-Derived Suppressor Cells in Cancer

Myeloid-derived suppressor cells (MDSCs) arise from myeloid progenitors in the bone marrow and, under the influence of tumor- and immune-cell-derived cytokines, chemokines, and growth factors, enhance immunosuppressive activity within the tumor microenvironment (TME). Noncoding RNAs (ncRNAs)-including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs)-have emerged as critical regulators of MDSCs biology. Recent evidence has shown that ncRNAs are intimately involved in MDSCs recruitment, differentiation, and suppressive function by modulating key signaling pathways, including STAT3, NF-κB, and PI3K/AKT. Mechanistically, ncRNAs act through epigenetic control (eg, histone modifications and chromatin remodeling), post-transcriptional regulation (eg, miRNA sponging), and fine-tuning of gene networks. These insights highlight RNA-based strategies that target ncRNAs to disrupt MDSCs-mediated immune suppression and potentiate antitumor immunity, while acknowledging ongoing challenges such as delivery specificity, stability, and off-target effects. This review synthesizes current understanding of how ncRNAs regulate MDSCs via major signaling axes and discusses implications for cancer progression and therapeutic development.