Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?

Abstract

Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56(bright) cells and an accumulation of highly differentiated CD56(dim) NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immunosurveillance. In AML patients, phenotypic changes in NK cells have been correlated with disease progression and survival. NK cell-based immunotherapy has emerged as a possibility for the treatment of AML patients. The understanding of age-associated alterations in NK cells is therefore necessary to define adequate therapeutic strategies in older AML patients.

Human CD56bright NK Cells: An Update

“…Overall, this study confirmed, as expected, the phenotypic characteristics of CD56 bright NK cells (1). It is known that the percentages and absolute numbers of NK cells increase in healthy ageing, but the decrease in the CD56 bright subset is interpreted as a lower output of such NK cells from the bone marrow (21).…”

NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia

“…These false negative cases strongly suggest that additional parameters are involved in relapse. The immune landscape of tumors is obviously more complex, [ 52 ] and beside alterations of NCR, additional anomalies have been described on both NK cell [ 53 – 55 ] and T cell subsets [ 56 , 57 ]. Clinical consequences of such immune profiles remain to be tested or validated.…”

Fragilidad en ancianos oncológicos en tratamiento con quimioterapia

“…Se sabe que el comportamiento de determinados tumores sufre alteraciones con la edad, presentando signos clínicos más agresivos por medio de alteraciones en su genoma, debido a la preparación menos eficiente del ácido desoxirribonucleico (ADN), edad biológica del tumor, sistema inmunológico comprometido, aumento de la carcinogénesis por influencia de la inflamación sistémica o resistencia a quimioterápicos 10 .…”