Restoration of natural killer cell cytotoxicity in the suppressive tumor microenvironment: novel approaches to treat AML

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy that is not completely cured in patients even after heavy chemotherapy treatments, resulting in the relapses of disease. Inactivation of immune cells such as natural killer (NK) cells is probably one of the causes of relapse. In this review, we described the role of NK cells in AML patients and outlined the current approaches to use of these cells in treatment of AML disease. Relevant articles from 1997 up to date, published in PubMed, were studied and compiled. The articles all contained the keywords: natural killer cell, acute myeloid leukemia, and treatment. Recognition of AML blast cells by NK inhibitory receptors and their interaction reduces NK cell cytotoxicity. On the other hand, NK cell immunotherapy along with administration of cytokines such as IL-2 and IL-15 can enhance the expression of activating receptors such as NKG2D and reduce the incidence of relapse in AML patients. Targeting NK inhibitory receptors and the use of IL-2 and IL-15 cytokine therapy can upregulate NK-activating receptors which decrease the relapse rate and improve the survival of patients with AML.