Circular RNAs in tumor biology and immunology: molecular mechanisms and therapeutic implications

Cancer immunotherapy has revolutionized oncology, yet its efficacy remains frequently constrained by the immunosuppressive tumor microenvironment (TME). Circular RNAs (circRNAs) are covalently closed RNA molecules generated through back-splicing. Their lack of free ends confers strong resistance to exonuclease degradation and high molecular stability. Within tumor cells, circRNAs govern multiple cancer hallmarks via diverse regulatory mechanisms. Beyond these cell-intrinsic functions, circRNAs can be secreted as intercellular messengers that enter and reshape the TME by modulating antitumor immunity. Clinically, the high stability of circRNAs in body fluids highlights their potential as non-invasive liquid biopsy biomarkers for cancer diagnosis and prognosis. Furthermore, beyond targeting endogenous circRNAs, engineered circRNAs encoding tumor antigens or immunomodulatory proteins represent a promising platform for cancer immunotherapy. In this article, we briefly summarize recent advances in the understanding of circRNAs in tumor biology and immunology.