Long Non-Coding RNAs in Natural Killer Cell Biology: Insights into Immune Regulation and Cancer

Background: Natural Killer (NK) cells are essential innate immune effectors that provide constant surveillance by inducing apoptosis in infected and malignant cells primarily through degranulation. Long non-coding RNAs (lncRNAs) are regulatory transcripts (>200 nucleotides) that modulate immune cell function, yet their specific roles in NK cells remain poorly characterized despite known effects on macrophages and lymphocytes.Objective: This review aims to consolidate current knowledge on the involvement of lncRNAs in NK cell biology, focusing on their regulatory impact on NK cell development, effector functions, and interactions within the tumor microenvironment (TME).Methods: We conducted a comprehensive narrative review of the literature, synthesizing findings related to lncRNA expression and function in hematopoiesis, NK cell maturation, cytotoxicity, cytokine production, and immune checkpoint modulation.Results: Our analysis reveals that lncRNAs are emerging as critical regulators across multiple stages of NK cell biology. They influence hematopoietic differentiation, modulate NK cell development and maturation, and directly affect cytotoxic degranulation and cytokine secretion. Importantly, lncRNAs are implicated in NK cell suppression within the TME, where they modulate immune checkpoint pathways and can either enhance or diminish the anti-tumor response.Conclusion: Elucidating the specific roles of lncRNAs in NK cells is crucial for a deeper understanding of the NK cell microenvironment. These insights hold significant potential for the development of novel NK cell-based immunotherapies and the identification of new biomarkers for cancer diagnosis and prognosis.