Efficacy and safety of natural killer cell therapy for the treatment of advanced non-small cell lung cancer: A meta-analysis and systematic review

To evaluate the efficacy and safety of natural killer (NK) cell therapy for the treatment of advanced non-small cell lung cancer (NSCLC). Relevant studies on NK cell therapy for advanced NSCLC were collected from PubMed, Scopus, Embase and the Cochrane Library up to August, 2024. Two reviewers independently screened the articles and retrieved the data using the Cochrane risk assessment tool. Meta-analysis was conducted with R (version 4.3.1). A total of nine trials were analyzed, including five phase 2 randomized controlled and four phase 1 studies. All were medium to high quality but exhibited high performance and attrition biases. NK cell treatment doses ranged from 1×10⁹ to 4×10⁹ cells for 2 or 3 cycles. In total, 324 patients with advanced NSCLC were included, comprising 199 who received NK cell therapy and 125 controls, all previously treated with platinum-based regimens. Meta-analysis demonstrated comparable disease control (OR = 2.68; 95% CI: 1.53-4.71) and 1-year survival (OR = 2.54; 95% CI: 1.28-5.02) between groups, with similar adverse events rates (OR = 1.37; 95% CI: 0.35-5.26). Subgroup analyses revealed no significant differences in efficacy. There was considerable heterogeneity among studies (I² = 0%-92.5%). Over 39 trials were registered, with only 12 marked as completed and none of the others released the outcome data. Current evidence suggests that NK cell therapy, either alone or in combination, may achieve disease control, survival outcomes and safety profiles that were comparable to existing treatments for advanced NSCLC. These findings remain exploratory and should be confirmed in larger, well-designed trials.