NK cells, as core components of innate immunity, exert direct anti-tumor effects without antigen priming, but their cytotoxicity is compromised by tumor-derived factors such as indoleamine 2,3-dioxygenase and prostaglandin E2 (PGE2), leading to reduced IFN-γ secretion and enhanced inhibitory receptor expression (Jing et al., 2024; Walker and Rotondo, 2004; Van Elssen et al., 2011). This evidence concerns the gene IFNG and neoplasm.