Abstract
MicroRNAs (miRNAs) have emerged as central regulators of antitumor immunity, influencing immune checkpoint signaling, immune cell differentiation, and intercellular communication within the tumor microenvironment. Although extensive preclinical evidence supports the immunomodulatory potential of miRNAs, their clinical translation remains challenging due to context dependence, network redundancy, delivery limitations, and safety concerns. Building upon recent advances in single-cell and spatial profiling, extracellular vesicle biology, and miRNA delivery technologies, this invited commentary critically examines how these developments extend current understanding of miRNA-mediated immune regulation in cancer. We highlight key conceptual and translational bottlenecks that continue to hinder therapeutic implementation and discuss why miRNAs are unlikely to achieve optimal efficacy as standalone immunotherapies. Instead, emerging evidence supports their greatest near-term clinical impact as adjunctive modulators and dynamic biomarkers within existing immunotherapeutic frameworks. By integrating mechanistic insights with translational perspectives, this commentary outlines future directions emphasizing cell-specific targeting, network-informed strategies, and biomarker-guided integration, providing a forward-looking framework for harnessing miRNAs in next-generation cancer immunotherapy.
Keywords
microRNAs, Cancer immunotherapy, Tumor microenvironment, Immune checkpoint regulation, Extracellular vesicles, Biomarker-guided therapy, Immune reprogramming