Immunotherapy is becoming one of the major tools in the clinic. The lymphocyte lineage natural killer (NK) cell present several advantages for its clinical use such as its low toxicity and the possibility of using it in allogeneic settings. We are devoted to generate NK-based immunotherapies in cancer and autoimmune diseases. Moreover, NK cells recognize stress signals in target cells. We have unveiled that variations in cell metabolism changes cell immunogenicity and recognition by NK cells as well as other cytotoxic lymphocytes. Hence, we investigate the molecular basis of these observations and the possibility of using metabolic drugs and NK-based immunotherapy. Moreover, because NK cells largely mediate the clinical effect of monoclonal antibodies (mAbs) functioning by antibody-dependent cell cytotoxicicty (ADCC), we are investigating the use of mAbs and NK in clinic. Finally, we are generating chimeric antigen receptors (CAR)-modified NK cells for autoimmune and cancer treatment.