B7-H6 Promotes Natural Killer Cell Cytotoxicity
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.1-2 Conversely, 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.
B7-H6 Induces Natural Killer Cell Cytotoxicity by Binding to the NKp30 Activating Receptor
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 of R&D Systems Recombinant Human B7-H6 and 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.
Assessment of the Bioactivity of R&D Systems Recombinant Human B7-H6 Protein
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 QuantikineTM ELISA Kit (R&D Systems, Catalog # DIF50). The ED50 for this effect is typically 0.6-3 μg/mL.