MicroRNAs in Cancer Immunology: Master Regulators of the Tumor Microenvironment and Immune Evasion, with Therapeutic Potential.

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.