B7-H4 Acts as a T Cell Co-inhibitory Receptor
B7-H4 Binds to an Unidentified Receptor and Inhibits T Cell Activation
Similar to B7-H3, B7-H4 is also highly expressed on various tumor cell types and tumor-associated macrophages and high expression correlates with tumor aggressiveness and reduced survival in a number of different types of cancer.1, 2 Although it has yet to be identified, a B7-H4 receptor appears to be expressed on activated T cells and to inhibit T cell proliferation, cytokine production, and cytolytic activity.3-5 Additionally, B7-H4 signaling is thought to promote the expansion of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells with immunosuppressive properties that accumulate in the tumor microenvironment.2 Similar to B7-H3, a soluble form of B7-H4 can be generated by ADAM-mediated ectodomain shedding, and high levels of soluble B7-H4 in the blood of cancer patients has been correlated with a poor prognosis.6
B7-H4 Delivers a Co-inhibitory Signal to Activated T Cells
B7-H4 binds to an unidentified receptor on activated T cells and inhibits T cell functions. Although the receptor for B7-H4 has yet to be identified, research suggests that it binds to a receptor expressed on activated T cells and inhibits T cell proliferation and effector functions.
Assessment of the Bioactivity and Purity of R&D Systems Recombinant B7-H4 Proteins
B7-H4 Inhibits IFN-gamma Secretion by Anti-CD3-Stimulated Human T Cells. Human T cells were treated with an immobilized Mouse Anti-Human CD3 epsilon Monoclonal Antibody (R&D Systems, Catalog # MAB100) and the indicated concentrations of Recombinant Rat B7-H4 Fc Chimera (R&D Systems, Catalog # 10085-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 1-6 μg/mL.
Assessment of the Purity of Avi-tag Biotinylated Recombinant Human B7-H4 by CE-SDS on the MauriceTM System. The purity of Avi-tag Biotinylated Recombinant Human B7-H4 Fc Chimera (R&D Systems, Catalog # AVI8870) was assessed by capillary electrophoresis (CE)-SDS on the Maurice System under reducing (R) and non-reducing (NR) conditions and visualized in Compass for iCE software. The gel view is shown as an inset with the relative migration time (RMT) on the electropherogram shown on the far right-hand side of the gel.
1. John, P. et al (2019) The B7x immune checkpoint pathway: from discovery to clinical trial. Trends Pharmacol. Sci. 40 883 PMID: 31677920
2. Janakiram, M. et al (2017) The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3. Immunol. Rev. 276 26 PMID: 28258693
3. Prasad, D.V. et al (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity 18 863 PMID: 12818166
4. Sica, G.L. et al (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18 849 PMID: 12818165
5. Zang, X. et al (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc. Natl. Acad. Sci. USA 100 10388 PMID: 12920180