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

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Oct;26(5):1317-1322. doi: 10.7534/j.issn.1009-2137.2018.05.010.
[Article in Chinese]

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • B7-H1 Antigen
  • Cell Line, Tumor
  • Humans
  • Interferon-gamma
  • Killer Cells, Natural*
  • Leukemia, Myeloid, Acute

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Interferon-gamma