B7-H6 Binds to the Natural Killer Cell Activating Receptor, NKp30

B7-H6, NKp30, and Natural Killer Cells

Unlike other B7 family proteins, B7-H6 is not expressed in normal human tissues under steady-state conditions, but it can be induced under inflammatory stress.¹ Accordingly, B7-H6 has been shown to be expressed on a variety of different tumor tissues.¹ B7-H6 binds to the NKp30 activating receptor on natural killer cells and induces cytotoxicity, thereby promoting anti-tumor immune responses.^1-2Conversely, it has also been shown that soluble B7-H6, which can be generated by ADAM-mediated ectodomain shedding, is associated with reduced expression of NKp30 and natural killer cell dysfunction in some forms of cancer.³ Additionally, B7-H6 was found to promote tumor cell proliferation and inhibit apoptosis in studies utilizing either human breast cancer or glioma cell lines, further suggesting that B7-H6 may be involved in driving tumorigenesis.^{4, 5} Similarly, high level expression of B7-H6 in human ovarian cancer was positively correlated with tumor progression and metastasis.⁶ Together, these observations suggest that B7-H6 may represent a promising therapeutic target.

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Binding of B7-H6 to the NK cell activating receptor, NKp30, induces NK cell cytotoxicity, promoting anti-tumor immunity.

B7-H6 binds to the NKp30 activating receptor on natural killer cells. Expression of B7-H6 is induced under inflammatory conditions and B7-H6 overexpression is frequently observed in tumors. Although B7-H6 binds to NKp30, an activating receptor expressed on natural killer cells, high level expression of B7-H6 in tumor tissues is commonly associated with tumor progression. Similarly, soluble B7- H6 has been demonstrated to down-regulate NKp30 expression on natural killer cells and inhibit natural killer cell activity, suggesting that B7-H6 may negatively regulate the immune response under certain conditions.

Analysis of the binding response between R&D Systems Recombinant Human B7-H6 and Recombinant Human NKp30 proteins.

NKp30 Binds to B7-H6. Recombinant Human B7-H6 (R&D Systems, Catalog # 9309-B7) was immobilized at 1 μg/mL, 100 μL/well and the indicated concentrations of Recombinant Human NKp30/NCR3 Fc Chimera (R&D Systems, Catalog # 1849-NK) were added. Recombinant Human NKp30 bound with an ED₅₀ of 0.02-0.1 μg/mL.

Analysis of the effect of R&D Systems Recombinant Human B7-H6 Fc Chimera protein on IFN-gamma secretion by NK-92 cells.

B7-H6 Induces IFN-gamma Secretion by NK-92 Cells. NK-92 human natural killer lymphoma cells were treated with the indicated concentrations of Recombinant Human B7-H6 Fc Chimera (R&D Systems, Catalog # 7144-B7). IFN-gamma secretion was measured using the Human IFN-gamma Quantikine^TM ELISA Kit (R&D Systems, Catalog # DIF50). The ED₅₀ for this effect is typically 0.6-3 μg/mL.