The effect of bone marrow humoral components in pediatric -cell acute lymphoblastic leukemia cases on natural killer cells

Acute lymphoblastic leukemia (ALL) is a hematological malignant disease of lymphoid precursor cells with uncontrolled proliferation and differentiation in bone marrow. Mostly occurring in children, ALL is the most common childhood cancer. B-ALL, generating from B lymphoid progenitor cells, is the most common form of the disease. Although the survival rate is high in patients treated with chemotherapeutic agents, side effects and resistance may occur. Thus, immunotherapy gains importance as a treatment option. Due to their importance in anti-cancer immunity, studies on natural killer (NK) cells in immunotherapy have increased. However, the efficiency of this treatment is lower than expected, which may be due to the immunosuppressive environment in bone marrow and circulation of B-ALL patients. Therefore, in our study, bone marrow plasmas of B-ALL patients were co-cultured for 24-72 hours with healthy cells. The subgroups, PD-1 expression, proliferation and IFN-g, IL-10 and TNF-a levels of NK cells were investigated. Experiments were compared to conditions with fetal bovine serum and bone marrow plasmas of patients without leukemia. Plasma IL-1b, IL-6, IL-10, IL-18, IFN-a2, IFN-b, IFN-g, TNF-a and GM-CSF levels were also measured. In the conditions with B-ALL plasmas, the ratios and proliferative capacities of NK cell subgroups were found to be decreased compared to the control groups, while PD-1 and intracellular IL-10 and TNF-a levels were increased. High IL-10 versus low IL-18 and IFN-g levels were detected in B-ALL plasmas. These findings indicate that humoral components in the bone marrow of B-ALL patients exert a suppressive effect on NK cells.