REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639763
This article is part of the Research TopicNoncoding RNAs in the Tumor Immune Microenvironment: Drivers of Solid Tumor Evolution and Therapeutic PotentialView all articles
Small Non-Coding RNAs: Key Regulatory Factors and Potential Therapeutic Targets in Tumor Immunity
Provisionally accepted
- Department of Gastroenterology, Affiliated Hospital, Ningbo University, Ningbo, China
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Tumor immunity has emerged as a focal point for cancer research. Although tumor immunotherapy represents a promising approach to cancer treatment, its effectiveness is often hindered by the heterogeneity of the tumor microenvironment (TME) and immune escape mechanisms. In recent years, small non-coding RNAs (sncRNAs) have attracted increasing attention in tumor immunology due to their essential role in gene regulation. This review systematically examines the multifaceted regulatory functions of sncRNAs in tumor immunity, with a focus on six major subtypes: microRNA, siRNA, piRNA, snoRNA, tsRNA, and snRNA. The molecular mechanisms by which these sncRNAs reshape the TME are discussed, including their roles in modulating immune cell differentiation (e.g., T cell polarization, macrophage phenotype transition), regulating immune checkpoint expression (PD-1/PD-L1, CTLA-4, Tim-3, LAG-3), and influencing tumor antigen presentation. This review also explores the dynamic network through which sncRNAs contribute to tumor immune escape. Furthermore, this study highlights the clinical potential of sncRNAs as liquid biopsy biomarkers and their application prospects in therapeutic strategies, such as targeted silencing of immunosuppressive molecules via nano-delivery systems, combination treatments with radiotherapy and chemotherapy, and Chimeric Antigen Receptor T-cell (CAR-T) therapy. Despite current challenges, including limited delivery efficiency and off-target effects, emerging technologies like AI-assisted sequence design and organ-on-a-chip models present new opportunities for clinical translation. This comprehensive review provides a theoretical foundation and translational insights for elucidating the functional network of sncRNAs in tumor immunology and advancing precise therapeutic interventions.
Keywords: small non-coding RNA, tumor immunity, Immune checkpoint, Tumor Microenvironment, tumor immune escape, Tumor immunotherapy
Received: 02 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Liu, Dong, Ye, Yan, Miao and Shao. 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: Yongfu Shao, Department of Gastroenterology, Affiliated Hospital, Ningbo University, Ningbo, China
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