Most promising approach include a) modified CAR-NK cells expressing chemokine receptors to improve migration and persistence of CAR-NK cells in the TME (107, 108); b) modified CAR-NK cells targeting Tregs and CAFs in TME to reduce the release of immune-suppressive cytokines and soluble factors (108); c) engineered CAR-NK cells expressing IL-12, IL-15, and IL-18 to boost NK cells antitumor activity and prolong their survival in the TME (108, 109); d) combination of CAR-NK cells with immune checkpoint inhibitors (ICIs) to prevent NK cells exhaustion and inhibition by cancer cells (107, 108). This evidence concerns the gene IL15 and cancer.