HLA and KIR polymorphisms affect NK-cell anti-tumor activity

Killer cell immunoglobulin-like receptors (KIRs) and their cognate human leukocyte antigen (HLA) ligands are key to the maintenance of natural killer (NK) cell tolerance. The gene complexes encoding both KIRs and HLA ligands are extremely polymorphic. Because the extent of NK cell inhibition varies with the allelic forms expressed, NK cell tolerance can be broken more easily in some individuals than in others. This explains why particular combinations of KIR and HLA genes are associated with an increased risk of autoimmune diseases or with more efficient antiviral responses. Breaking of NK cell tolerance might be prerequisite to kill leukemic blasts. At present, there are ample indications that NK cells can eradicate acute myeloid leukemia blasts in patients with a favorable combination of HLA and KIR genes. Selecting these individuals for clinical trials should give insight into the feasibility of anti-tumor therapy mediated through NK cells.