Given UBE2S’s established roles in tumor progression48–51 and its reported crosstalk with the STAT3 pathway52,53, and considering the known regulation of NK cell STAT3 by cytokines including IL-629,54,55 and its involvement in cytokine-driven NK receptor downregulation (e.g., in esophageal squamous carcinoma29), we hypothesized and subsequently validated that IL-6 impairs NK cell function within the tumor microenvironment by activating the STAT3-UBE2S axis to enhance NKp30 ubiquitination and degradation. This evidence concerns the gene UBE2S and neoplasm.