Changing in the regulatory system of NK cells in patients with AML post activation in vitro
Fas ligand and TRAIL as death ligands on the surface of NK cells can activate target killing by attaching death receptors on the target cell, which activates NK cell cytotoxicity through caspase-8 dependent pathway extrinsic apoptosis 18. We expected that Fas ligand expression upregulated in activated groups. However, its over-activated when the NK-cells were treated with IL-15 + Hsp70 (p<0.0001,Fig. 5A ). Similarly, TRAIL expression also increased in IL-15 + Hsp70 group but it was just significant to IL-15 + PD-1 blocker + Hsp70 group (p<0.0089, Fig. 5B ). Studies showed that PI3K–AKT–mTOR pathway is the main pathway in regulating the development, differentiation, and activation processes of immune cells like NK cells 19. Also, PIK3CB, as a subunit of (phosphoinositide 3-kinase) PI3K, has a crucial role in NK cell cytotoxicity 20. In the assessment of the AKT-1 gene, it seems that the PD-1 blocker in combination of IL-15 has the potential to increase its expression levels (Fig. 5C ). Also, the increased expression level of PIK3CB in the IL-15 + PD-1 blocker treated NK cells was significant in comparison to other groups (p<0.01, Fig. 5D ) excluding the IL-15 + PD-1 blocker + Hsp70 group which was not significant (p>0.05,Fig. 5D ).