Natural killer cell therapies in cancer: innovations, challenges, and future directions

Introduction: Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contribute to immune surveillance and regulation. Their therapeutic potential lies in their ability to act across donor barriers with a reduced risk of graft-related complications; however, clinical translation remains challenging due to tumor immune evasion and limited persistence in suppressive environments. Areas covered: This review summarizes the biological roles of NK cells in cancer immunity and examines recent therapeutic approaches that harness their cytotoxic and regulatory properties. We discuss barriers to clinical application, including immune suppression, antigen loss, and manufacturing limitations. In addition, we highlight emerging strategies, such as gene editing, rational combination therapies, and standardized clinical trial designs, aimed at improving therapeutic efficacy. Expert opinion: NK cell-based therapies represent a promising avenue in cancer immunotherapy but require carefully designed solutions to overcome their inherent limitations. Advances in biomarker-guided patient selection, integration with existing treatment modalities, and international collaboration will be critical for translating NK cell biology into effective and durable clinical outcomes.