MicroRNA-targeted reprogramming of CD8+ T cells against cancer.

This scoping review highlights the critical role of microRNAs (miRNAs) in mediating the bidirectional crosstalk between CD8+ T cells and tumor cells within the immunosuppressive tumor microenvironment (TME). Specific miRNAs (e.g., miR-155, miR-340-5p) orchestrate CD8+ T cell function by fine-tuning immune checkpoints (PD-1/PD-L1), metabolic reprogramming, and epigenetic states. Conversely, CD8+ T cells influence tumor behavior via exosomal miRNA transfer (e.g., miR-765). Our analysis reveals both pan-cancer mechanisms, such as PD-1/PD-L1 regulation, and tissue-specific miRNA functions (e.g., miR-143 in melanoma). To overcome translational challenges like off-target effects, innovative delivery strategies using lipid nanoparticles and engineered exosomes are being developed. This review provides a mechanistic framework for miRNA-mediated interactions, offers clinical insights for novel combination therapies, and assesses future directions, thereby advancing the development of precision immunotherapies.