MicroRNAs Modulating Cancer Immunotherapy Mechanisms and Therapeutic Synergies
Naorem Loya Manganga, Samantha K. Gargaszb, S. Muruganc, Munish Kumard, Girish C. Shuklab, Sivakumar Vijayaraghavalua c✉
- aDepartment of Life Sciences (Zoology), Manipur University (A Central University), Imphal 795003, Manipur, India
- bCenter for Gene Regulation in Health and Disease, Department of Biological, Geo and EVS Sciences, 2121 Euclid Ave., Cleveland, OH 44115, USA
- cDepartment of Medical Sciences and Technology, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India
- dDepartment of Biochemistry, Faculty of Science, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
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Abstract
Simple Summary Immunotherapy has transformed cancer treatment, but many patients do not respond or develop resistance. microRNAs (miRNAs) play a crucial role in regulating the interaction between cancer cells and immune cells. miRNA can turn immune checkpoint signals on or off, alter the behavior of T cells and macrophages, and travel in tiny vesicles between cells to influence the tumor environment. Because of these functions, miRNAs are being studied as biomarkers to predict who will benefit from immunotherapy, and as drugs themselves, either to block harmful miRNAs or replace protective ones. Although the first clinical trials faced safety and delivery challenges, new technologies such as nanoparticles and exosome-based systems are making miRNA therapies more feasible. This review synthesizes the latest evidence on how miRNAs can enhance cancer immunotherapy and explores future directions for translating these findings into clinical practice. Abstract Cancer immunotherapy has transformed oncology, but lasting responses are still limited due to resistance mechanisms within the tumor microenvironment. MicroRNAs (miRNAs) have emerged as critical regulators of immune checkpoint pathways, antigen presentation, T-cell activity, and macrophage polarization. By modulating both tumor-intrinsic and immune cell–intrinsic processes, miRNAs influence the efficacy of immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapies. Additionally, circulating and exosomal miRNAs are being investigated as minimally invasive biomarkers to predict patient response and resistance to immunotherapy. Clinical trials of miRNA-based treatments, including mimics and inhibitors, have highlighted both the promise and challenges of translating these molecules into clinical use. Advances in delivery systems, RNA chemistry, and combinatorial strategies are paving the way for their integration into precision immuno-oncology. This review offers a comprehensive overview of the mechanistic, biomarker, and therapeutic roles of miRNAs in cancer immunotherapy, highlighting ongoing clinical progress and prospects.
TL;DRThis review synthesizes the latest evidence on how miRNAs can enhance cancer immunotherapy and explores future directions for translating these findings into clinical practice, highlighting ongoing clinical progress and prospects. (Semantic Scholar)