CRISPR/Cas9-directed deletion of the cytokine-inducible SH2 gene (CISH) in murine NK cells resulted in hyperresponsiveness of CISH−/− NK cells subjected to IL-15 stimulation, with increased expansion rates in comparison with wild-type NK cells, enhanced cytotoxicity towards tumor cells in vitro, and reduction in metastasis in melanoma-, prostate-, and breast-cancer-transplanted mice [389]. Here, IL15 is linked to neoplasm.