Human Cytokine-Induced Memory-Like Natural Killer Cells

J Innate Immun. 2015;7(6):563-71. doi: 10.1159/000382019. Epub 2015 Apr 30.


Natural killer (NK) cells are innate lymphoid cells that are important for host defense against infection and mediate antitumor responses. Recent reports from several laboratories have identified that NK cells can remember a prior activation event and consequently respond more robustly when restimulated, a property termed innate NK cell memory. NK cell memory has now been identified following hapten exposure, viral infection, and combined cytokine preactivation with IL-12, IL-15, and IL-18. Many questions in the field remain regarding the cellular and molecular mechanisms regulating memory NK cells and their responses, as well as their formation and function in mice and humans. Here we review our current understanding of cytokine-induced memory-like (CIML) NK cells that are generated by combined preactivation with IL-12, IL-15, and IL-18. These cells exhibit enhanced NK cell effector functions weeks after the initial cytokine preactivation. Further, we highlight the preclinical rationale and ongoing therapeutic application of CIML NK cells for adoptive immunotherapy in patients with hematologic malignancies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytokines / immunology*
  • Haptens / immunology
  • Hematologic Neoplasms / immunology*
  • Hematologic Neoplasms / pathology
  • Humans
  • Immunity, Cellular*
  • Immunologic Memory*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Mice
  • Virus Diseases / immunology*
  • Virus Diseases / pathology


  • Cytokines
  • Haptens