Zare Erfan, Yaghoubi Seyyed Mohammad, Khoshnazar Maedeh, Jafari Dargahlou Sina, Machhar Janvhi Suresh, Zheng Zihan, Duijf Pascal H G, Mansoori Behzad
Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil 5371713111, Iran.
Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil 5618985991, Iran.
Cancers (Basel). 2025 Jun 27;17(13):2172. doi: 10.3390/cancers17132172.
MicroRNAs (miRNAs) are pivotal modulators of tumor progression and immune function. Given the central role of the immune system in recognizing and eliminating malignant cells, understanding how miRNAs influence immune responses has become essential for advancing cancer therapy. This review explores the emerging roles of miRNAs in orchestrating cancer immunology, emphasizing their regulation of tumor immune surveillance, immune equilibrium, immune evasion, and immunometabolism. We further illustrate how specific miRNAs modulate the tumor microenvironment by shaping immune cell phenotypes, cytokine networks, and antigen presentation. Some miRNAs enhance cytotoxic T lymphocyte activity, while others promote immune escape by expanding regulatory T cells and myeloid-derived suppressor cells. miRNAs also regulate immune checkpoints (e.g., PD-L1 and CTLA-4), metabolic reprogramming, and stress responses that collectively influence tumor immunogenicity. Additionally, miRNAs are gaining traction as biomarkers for immune activity and predictors of immunotherapy response. Therapeutically, miRNA mimics and inhibitors can enhance anti-tumor immunity, particularly when combined with advanced delivery platforms or immune checkpoint inhibitors. However, challenges such as delivery specificity, off-target effects, and the context-dependent nature of miRNA activity remain significant barriers to clinical translation. Despite shortcomings, miRNAs represent a class of immune regulators with substantial therapeutic potential. Accelerated progress in miRNA-guided therapies is anticipated through deepening insights into miRNA regulatory networks, coupled with integrative multi-omics and AI-driven analytical frameworks. Altogether, miRNAs are a promising frontier in next-generation cancer immunotherapy and precision oncology.
微小RNA（miRNA）是肿瘤进展和免疫功能的关键调节因子。鉴于免疫系统在识别和清除恶性细胞中的核心作用，了解miRNA如何影响免疫反应对于推进癌症治疗至关重要。本综述探讨了miRNA在协调癌症免疫学中的新作用，强调了它们对肿瘤免疫监视、免疫平衡、免疫逃逸和免疫代谢的调节。我们进一步阐述了特定的miRNA如何通过塑造免疫细胞表型、细胞因子网络和抗原呈递来调节肿瘤微环境。一些miRNA增强细胞毒性T淋巴细胞活性，而另一些则通过扩大调节性T细胞和髓源性抑制细胞来促进免疫逃逸。miRNA还调节免疫检查点（如PD-L1和CTLA-4）、代谢重编程和应激反应，这些共同影响肿瘤免疫原性。此外，miRNA作为免疫活性的生物标志物和免疫治疗反应的预测指标正越来越受到关注。在治疗方面，miRNA模拟物和抑制剂可以增强抗肿瘤免疫力，特别是与先进的递送平台或免疫检查点抑制剂联合使用时。然而，诸如递送特异性、脱靶效应以及miRNA活性的背景依赖性等挑战仍然是临床转化的重大障碍。尽管存在缺点，miRNA代表了一类具有巨大治疗潜力的免疫调节因子。通过加深对miRNA调控网络的认识，结合综合多组学和人工智能驱动的分析框架，有望在miRNA引导的治疗方面取得更快进展。总之，miRNA是下一代癌症免疫治疗和精准肿瘤学中一个有前途的前沿领域。
