MicroRNA-mediated regulation of natural killer cells development, effector functions, and antitumor responses

Cancer Cell Int. 2025 Dec 2;25(1):429. doi: 10.1186/s12935-025-04078-1.

Abstract

Natural killer (NK) cells represent a fundamental aspect of the innate immunity. These cells considered as a vital part of tumor immunosurveillance by directly eliminating cancer cells and releasing cytokines. Their role is closely controlled through the equilibrium between activating and inhibitory signals. MicroRNAs (miRNA), being short non-coding RNAs, involve in controlling the differentiation, maturation, and effector responses of NK cells. Here, we highlight the functions of miRNAs in controlling NK cell lineage commitment, subset differentiation, cytotoxicity, and immune checkpoint expression. Additionally, it explores how tumor-derived factors, such as hypoxia, modulate miRNA expression, thereby impairing NK cell activity within the tumor microenvironment (TME). Additionally, we summarized how manipulating miRNA pathways could improve NK cell-based immunotherapies.

Keywords: Cancer immunotherapy; MicroRNAs (miRNAs); Natural killer (NK) cells; Tumor immunity; Tumor microenvironment (TME).

Publication types

  • Review