sdf-1α reduces human natural killer cell cytotoxicity against chronic myelogenous leukemia k562 cells

Stromal cell-derived factor-1 alpha (sdf-1α) has been shown to be up-regulated in a variety of malignancies. so that, its expression is associated with poor prognosis and invasiveness. natural killer (nk) cells are important effector cells against virus-infected and transformed cells. especially they play a key role in tumor immune surveillance. whereas it was not well understood whether sdf-1α modulates anti-tumor immune response or not, the purpose of the present study was to investigate the effect of sdf-1α on the cytotoxic properties of peripheral blood nk cells. human peripheral blood nk cells were freshly isolated using macsxpess system and cultured in the presence or absence of recombinant human sdf-1α or sdf-1α plus cxcr4 antagonist, amd3100. cd107a degranulation assay was conducted through the co-culture of nk cells with k562 cells. the percentage of cd107a positive cells was assessed by flowcytometry. effect of sdf-1α was also examined on the mrna levels of nkg2a and nkg2d as indicator examples of nk cell inhibitory and activating receptors, respectively. sdf-1α significantly decreased the degranulation activity of nk cells (p=0.04). the mrna content of nkg2d was down-regulated under the influence of sdf-1α (p=0.03). moreover, amd3100 exhibited a trend in recovering the nkg2d mrna level to its un-treated state (p=0.05). the present study reveals that sdf-1α has a negative impact on nk cell activity and might is involved in tumor immune-suppression. thus, it can be concluded that microenvironment manipulations targeting sdf-1α may reinforce current cancer therapies by disturbing one of the immune-suppressive axes in the cancerous milieu.