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Emerging roles of circular RNA in cancer immunotherapy: From molecular mechanisms to therapeutic strategies
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DOI：10.1016/j.gendis.2026.102369.png)
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Abstract
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Circular RNAs (CircRNAs) are a distinct class of endogenous non-coding RNAs, formed through the back-splicing of precursor mRNAs followed by intricate post-transcriptional processing. These molecules are characterized by their covalently closed, continuous structure, which lacks 5' caps and 3' poly-A tails. This unique structure endows circRNAs with remarkable stability and resistance to exonucleolytic degradation, facilitating their prolonged regulatory roles within cellular microenvironments. Growing evidence highlights the crucial role of circRNAs as key regulators in tumorigenesis, metastatic progression, and immune evasion, mediated through diverse mechanisms such as miRNA sponging, protein scaffolding, and direct translation. This review systematically introduces the multidimensional roles of circRNAs in cancer immunotherapy, providing a comprehensive analysis from molecular mechanisms to clinical translation. It focuses on the molecular networks through which circRNAs influence the immune therapy response by regulating the intrinsic properties of tumor cells and remodeling the tumor microenvironment. Additionally, the review discusses the clinical potential of circRNAs as novel biomarkers, therapeutic targets, and drug delivery vehicles, with a particular emphasis on their strategic value in overcoming resistance to immunotherapy. Finally, the article comprehensively analyzes the technical challenges associated with the clinical translation of circRNAs and proposes innovative solutions, thereby offering a theoretical framework and translational pathway for circRNA-based precision immunotherapy strategies.
Keywords:
CircRNAs
Immunotherapy
Immune checkpoint therapy
Tumor microenvironment
CircRNA vaccine
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