Circular RNAs in tumor immunity and immunotherapy of breast cancer

Abstract

As the stable and conserved circular non-coding RNAs, circular RNAs (circRNAs) have assumed growing significance in regulating breast cancer immunity and immunotherapy. This review focuses on elucidating the molecular mechanisms through which circRNAs influence the efficacy of breast cancer immunotherapy. Specifically, circRNAs modulate the levels and stability of critical immune checkpoints, including PD-L1 and various cytokines. They achieve this by acting as competing endogenous RNAs (ceRNAs) to sequester miRNAs, functioning as protein scaffolds, and thereby modulating gene expression and tumor immune evasion. Furthermore, circRNAs are capable of facilitating communication between tumor cells and immune cells. In addition, it can be translated into proteins that aid in remodeling the tumor immune microenvironment. These changes may include driving the polarization of immunosuppressive M2-type macrophages, while suppressing the infiltration and functional activity of cytotoxic T cells and natural killer cells. These findings highlight the significant promise of circRNAs serving as novel biomarkers and candidate therapeutic targets. Targeting specific circRNAs is anticipated to emerge as an effective approach for enhancing the efficacy of current immune checkpoint inhibitors, potentially helping to overcome drug resistance encountered in immunotherapy. Furthermore, it offers potential for the development of novel circRNA-based vaccines. Collectively, these advancements pave the way for improving the prognosis of breast cancer immunotherapy and open new avenues for future research and clinical translation.