Natural Killer cells at war: Unravelling the role of NK cells in acute myeloid leukemia

Natural Killer (NK) cells play a major role in the immune response against cancer, including hematological conditions such as myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). This review explores the impact of the leukemic microenvironment on NK cell subsets in AML and MDS, shedding light on their potential implications in disease progression. In AML, studies have revealed a maturation blockade of NK cells in the altered bone marrow microenvironment, while NK cells from peripheral blood have the tendency to differentiate all the way to the final stages. The leukemic microenvironment not only affects NK cells but other immune compartments as well, including T cells. Therefore, a phenomenon of effector cell exhaustion has been described for both T cells and NK cells in AML, leading to compromised immune responses. Furthermore, altered expression of inhibitory receptors, such as NKG2A and KIR, on NK cells in AML and MDS suggests a potential involvement of leukemic cells in the preferential expression of key inhibitory molecules on the surface of these effectors. The dysregulated cytokine milieu within the leukemic microenvironment may account for the changes in receptor expression patterns, influencing both NK cell cytotoxicity and secretory functions. In conclusion, the leukemic cells and altered microenvironment have profound effects on NK cell subsets in both AML and MDS, affecting their maturation, function, and phenotype. Understanding these interactions may provide insights into novel therapeutic approaches to enhance the anti-tumoral immune response and improve outcomes for these patients.