REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicExploring the Tumor Microenvironment: From Immune Dynamics to Therapeutic OpportunitiesView all articles
Dual-faced circRNAs: Orchestrating immunosuppression and activation in the lung cancer microenvironment
Provisionally accepted
- 1Jilin University, Changchun, China
- 2Qilu Hospital of Shandong University Qingdao, Qingdao, China
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Circular RNAs (circRNAs), a class of non-coding RNAs characterized by covalently closed loop structures, have emerged as key regulators in the tumor immune microenvironment (TIME) of lung cancer, owing to their high stability, tissue-specific expression, and multi-dimensional regulatory capabilities. This review systematically synthesizes the latest research progress and elucidates the processes by which circRNAs regulate the functional states of immune cells in the TIME through diverse molecular mechanisms, including acting as competing endogenous RNAs (ceRNAs) to sequester microRNAs (miRNAs), interacting with RNA-binding proteins (RBPs), and in some cases, encoding functional polypeptides. CircRNAs possess bidirectional regulatory capacities: they can promote tumor immune evasion by modulating the expression of immune checkpoint molecules, influencing the infiltration and activity of effector immune cells (e.g., CD8⁺ T cells), recruiting immunosuppressive cells (e.g., regulatory T cells, M2-type macrophages), and regulating immune signaling pathways; meanwhile, they can also activate anti-tumor immune responses. Furthermore, the review explores the potential of circRNAs as liquid biopsy biomarkers for lung cancer diagnosis and prognosis, as well as their translational prospects in therapeutic strategies including vaccines, circRNA-enhanced CAR-T therapy, and formulations encoding immunomodulatory factors. Despite challenges such as complex mechanisms, low delivery efficiency, and safety concerns, the development of multi-omics technologies, novel delivery systems, and gene-editing tools provides directions for the development of precision therapies targeting circRNAs, which aim to reshape the lung cancer immune microenvironment and overcome immunotherapy resistance.
Keywords: circular RNAs, immune microenvironment, Immune checkpoint, Immunotherapy resistance, CAR-T therapy
Received: 16 Sep 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Li, Zhang, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yicun Wang, wangyicun@jlu.edu.cn
Chunyan Li, lichunyan769@163.com
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