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Cancer remains one of the most challenging health issues worldwide. Thus, there is an urgent need to discover effective treatments for cancer. Immune checkpoint blockade targeting the PD-1/PD-L1 axis has revolutionized cancer therapy, yet resistance and limited clinical efficacy remain significant challenges. Emerging evidence highlights ncRNAs as upstream regulators of PD-1/PD-L1, offering novel therapeutic opportunities. This review systematically examines the role of miRNAs, lncRNAs, and circRNAs in modulating PD-1/PD-L1 signaling across diverse cancers, emphasizing their mechanisms and clinical implications. We further discuss the potential of ncRNAs as biomarkers and therapeutic targets to overcome immune evasion and enhance immunotherapy efficacy.
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