Aging of natural killer cells in acute myeloid leukemia

Abstract

Aging is associated with changes in the immune system involving both adaptive and innate immunity. Immunosenescence refers to the deterioration of the immune system function associated with aging. Natural killer (NK) cells are innate lymphoid cells specialized in killing tumor cells as well as virus-infected cells without the requirement of prior sensitization. NK cells are also involved in regulating immune function as they produce several cytokines and chemokines. NK cell immunosenescence affects the frequency, phenotype, and subset distribution of human NK cells. A decreased expression of activating receptors is observed in the elderly that may contribute to the decline of NK cell function. It has been proposed that the failure of tumor immunosurveillance may be partly responsible for the age-associated increase in cancer incidence. Acute myeloid leukemia (AML) is a disease of older adults with a median age at diagnosis usually over 65 years old. NK cells in AML patients show a reduced expression of several activating receptors that impair NK cell function. Low level of expression of activating receptors such as NKp46 has been correlated with disease progression and patient survival. KIR-HLA class I receptor-ligand mismatch is associated with a graft versus leukemia effect in haploidentical hematopoietic stem cell transplantation supporting the role of NK cells in AML control. Thus, NK cell-based immunotherapy emerges as a novel treatment for AML patients. However, a better understanding of age-associated changes on NK cell phenotype and function is required to delineate adequate therapeutic strategies in older AML patients.