Advances in the mechanisms of exosome-derived non-coding RNAs regulating T-cell infiltration in tumors

Effective anti-tumor immunity is based on T-cell infiltration and functional integrity inside the tumor microenvironment (TME). By transporting bioactive non-coding RNAs (ncRNAs), such as lncRNAs, miRNAs, and circRNAs, exosomes, as essential intercellular communication mediators, have become master regulators of the TME. Of note, however, the vast majority of current evidence is derived from studies on exosomal miRNAs, whereas other non-coding RNA classes (lncRNAs, circRNAs, etc.) remain less systematically characterized. This review systematically elucidates the molecular circuitry through which exosomal ncRNAs orchestrate T-cell dynamics. We discuss how these ncRNAs facilitate T-cell exclusion and exhaustion by manipulating the PD-1/PD-L1 checkpoint path, reprogramming myeloid and stromal cells to induce an immune suppressor niche, directly subverting T-cell metabolic fitness and effector functions. Specifically, we highlight the distinct yet synergistic roles of exosomal miRNAs in post-transcriptional silencing, lncRNAs in protein scaffolding and epigenetic remodeling, and circRNAs as potent miRNA sponges and protein modulators.