IL15 and in situ carcinoma: IL-15 substantially improved CB-NK use in NK cells, especially when combined with the knockout of the CIS gene.488 However, reports suggest that secreted IL-15 expands primary and CB-NK cells but causes severe487 to lethal toxicity and cytokine release syndrome in animal models.489 Others reported that NK cell chronic stimulation by IL-15 leads to exhaustion by a metabolic defect.490 IL-12 produced by DCs and macrophages stimulates NK cells and leads to IFNγ production, which enhances DCs activation and induces T-cell polarization.