Revealing miRNAs' Janus-Faced Nature: Transforming Cold Tumours into Immunotherapy Hotspots and Overcoming Chemoresistance.

Shinjini Sen, Ranu Nayak, Banashree Bondhopadhyay, Sudeep Bose
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Abstract

MicroRNA (miRNA) modulation has emerged as a promising strategy in cancer immunotherapy, particularly in converting "cold" tumors with limited immune cell infiltration into "hot" tumors responsive to immunotherapy. miRNAs regulate immune cell recruitment and activation within the tumor microenvironment, influencing tumor behavior targeting specific miRNAs in cold tumors aims to enhance the immune response, potentially improving therapeutic efficacy. Despite ongoing research challenges, such as tumor complexity and treatment resistance, miRNA-based therapies offer personalized approaches with potential ethical considerations. Advances in miRNA profiling may enable early cancer detection and tailored treatments, underscoring its role in future oncology. This review sheds light on the role of miRNA in cold and hot tumor microenvironments, how they modulate depending on the tumor niche and the current research challenges in implementing miRNA-based therapies include the complexity of tumors and their heterogeneity, which makes it difficult to identify the most relevant miRNAs to target. Additionally, treatment resistance can develop over time, reducing the effectiveness of miRNA modulation. Despite these challenges, ongoing research and advancements in miRNA profiling hold promise for overcoming these obstacles and improving the outcomes of cancer immunotherapy. To overcome the challenges of identifying relevant miRNAs to target, researchers can employ high-throughput sequencing techniques to comprehensively profile miRNA expression in different tumor subtypes. They can also utilize bioinformatics tools and databases to analyze the vast amount of miRNA-related data and identify potential candidate miRNAs. Furthermore, collaborations between scientists and clinicians can help validate the functional significance of identified miRNAs and their potential as therapeutic targets.

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