Secreted β(3)-Integrin Enhances Natural Killer Cell Activity against Acute Myeloid Leukemia Cells

Integrins are a large family of heterodimeric proteins that are involved in cell adhesion, migration, and proliferation. Integrin diversity and function is regulated by alternative splicing. Membrane-bound and truncated β(3)-integrins were shown to be key players in cancer metastasis. However, the immunomodulatory functions of the soluble (s) β(3)-integrin have not been investigated yet. In this study, we described a novel form of sβ(3)-integrin in acute myeloid leukaemia (AML) patients. Furthermore, we assessed the role of the sβ(3)-integrin in the modulation of natural killer (NK)-cell activity. Levels of sβ(3)-integrin were analysed in plasma samples of 23 AML patients and 26 healthy donors by ELISA. The capacity of sβ3-integrin to regulate NK cell activity was investigated using proliferation, cytokine secretion, and cytotoxicity assays. Circulating sβ(3)-integrin was detected in the plasma of 8 AML patients. NK cells showed significantly higher proliferation rates after stimulation with sβ(3)-integrin and IL-2, IL-15 (73%). Significant increases in the NK cells’ secreted levels of TNF-α, IFN-γ were measured in presence of sβ(3)-integrin. In addition, sβ(3)-integrin caused the upregulation of Granzyme B transcripts levels as well as FasL expression levels in NK cells. Most importantly, significantly higher K562 or AML blast target cell lysis rates were observed when NK cells were exposed to sβ(3)-integrin. This study reports the identification of a novel sβ(3)-integrin in AML patients and provides novel insights into its role in the immunomodulation of NK cell activity.