Effect of PD-L1 Expression on Activity of NK Killing AML Cell Lines and Its Mechanisms

Abstract

To expolore the effect of programmed death receptor ligand 1 (PD-L1) expression level on killing effect of different cell lines of acute myeloid leukemia (AML) and its possible mechanism. Peripheral blood from healthy individuals was collected routinely; NK cells were isolated using immunomagnetic beads; PD-L1 expression level was detected by flow cytometry; the killing effect of NK cells on acute myelogenous leukemia cell lines was evaluated with LDH release method and monoclonal antibody blocking experiment; the expression levels of IFN-γ and IL-2 in the supernatants from the co-cultured effector/targer cells were measured by ELISA. The ratio of CD3-CD56+NK cells increased from （12.44±3.48）% to (71.29±5.65）%. The flow cytometry showed that KG-1a cells lowly expressed PD-L1 (8.35±4.12)%, but the THP cells a highly expressed PD-L1 (76.42±26.54)%. Meanwhile, the NK cells displayed a more efficient killing effect on KG-1a cells than that of THP1 cells (P<0.05). Moreover, PD-L1 monoclonal antibody could reinforce NK cell killing effect and, promote the secretion of IFN-γ and IL-2 in 5 acute myelogenous leukemia cell lines to varying degree. The killing effect of NK cells on acute myelogenous leukemia cell line is inversely proportional to PD-L1 expression; blocking PD1/PD-L1 binding can significantly enhance the killing efficiency of effector-target cells, which way be related with promoting the release of IFN-γ and IL-2.