receptor Ig). Pre-activation of NK cells by the cytokines IL-12/18 plus IL-15 or by engagement of FcγRIII/CD16 via therapeutic antibodies can induce similar memory-like functions: an enhanced proliferative capacity toward IL-2 due to CD25 up-regulation as well as a strengthened responsiveness to restimulation by tumor cells. Importantly, both memory-like functionalities are antigen-unspecific and mean “remembering” a previous state of increased activation caused by cytokine exposure or stimulation via activating NK cell receptors. In humans Unique and expanded adaptive NK cell populations were observed in peripheral blood in humans that have been previously infected with Human Cytomegalovirus (HCMV). These NK cells bear activating MHC class I-binding receptors, typically CD94/NKG2C, demonstrate reduced activation and degranulation in response to activated autologous T cells and they are CD56dim CD16+. In comparison to CD56dim cNK cells, adaptive NK cells generally show decreased expression of surface CD7, CD161, NKp30, NKp46, and SIGLEC-7 but demonstrate retained or even higher expression of CD2, CD57, and CD85j (ILT2, LILRB1). None of these surface marker expression patterns are inherently specific for adaptive NK cells, but together they may help to identify discrete populations of adaptive NK cells. Human adaptive NK cells have the hypomethylated region of IFN-γ promoter. After stimulation through CD16 ligation adaptive NK cells produce large amounts of IFN-γ and also extensively proliferate. The cytotoxicity of adaptive NK cells remains a constant question in this field. It had been indicated similar or reduced degranulation of CD107a as compared to cNK cells after CD16 ligation or stimulation with antibody-coated tumor targets. The discovery of memory in the human NK compartment makes us wonder whether it could be harnessed by vaccination. This could be particularly effective in HIV infections where CD4+T cells get rapidly depleted as it provides an alternative where B and T cells cannot be harnessed. Therapeutic potential The clinical application of NK cells with memory-like properties can significantly increase the efficiency of these cells and pave the way for the new NK cell-based clinical approaches for the cancer treatment. Adaptive NK cells can mediate the enhanced antitumor effects, that may be due to their increased cytotoxicity, high IFN-γ production capacity, and persistence in large numbers in the host. Clinical use of allogeneic NK cells is promising for the treatment of leukemia. KIR-ligand mismatch has a beneficial effect on the alloreactivity of donor NK cells against recipient leukemia. Besides, it has been shown that the adoptive transfer of