Our results demonstrated that engineered CAR-NK cells expressing IL-21 were associated with the upregulation of metabolic-related genes PKM and SLC2A1, as well as cytotoxicity-related genes GZMB, GMZA, IFNG, TNFRSF8, PRF1. This suggests that constructing IL-21-secreting CAR-NK cells enhances their metabolic fitness and endows them with superior anti-tumor function. Here, PRF1 is linked to neoplasm.