title: Cytokines reinstate NK cell-mediated cancer immunosurveillance.
abstract: In healthy individuals, cells that lose expression of MHC class I molecules are quickly targeted for elimination by NK lymphocytes. A paradox in cancer immunology is the observation that many tumor cells often have a drastic reduction of MHC class I molecules, yet these cells are not eliminated by NK cells, as they should be. In this issue of the JCI, Ardolino et al. demonstrate that NK cells that infiltrate MHC class I-deficient tumors acquire an anergic state that can be reversed by particular combinations of exogenous cytokines. These results indicate that IL-12 plus IL-18 or a recombinant interleukin engineered to stimulate the IL-2 receptor β/γ heterodimer (but not the IL-2 receptor α/β/γ complex) have the potential to be used clinically to reinstate immunosurveillance against MHC class I-deficient tumors.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*
chemical_list: D020382:Interleukin-18; D007376:Interleukin-2; D018664:Interleukin-12