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Trends Immunol. 2013 Nov;34(11):556-63. doi: 10.1016/ Epub 2013 Aug 13.

B7 family checkpoint regulators in immune regulation and disease.

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Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, Norris Cotton Cancer Centre, 1 Medical Center Drive, Lebanon, New Hampshire 03756, USA.


Fine-tuning the immune response and maintaining tolerance to self-antigens involves a complex network of co-stimulatory and co-inhibitory molecules. The recent FDA approval of ipilimumab, a monoclonal antibody blocking cytotoxic T lymphocyte antigen (CTLA)-4, demonstrates the impact of checkpoint regulators in disease. This is reinforced by ongoing clinical trials targeting not only CTLA-4, but also the programmed death (PD)-1 and B7-H4 pathways in various disease states. Recently, two new B7 family inhibitory ligands, V-domain Ig suppressor of T cell activation (VISTA) and B7-H6 were identified. Here, we review recent understanding of B7 family members and their concerted regulation of the immune response to either self or foreign pathogens. We also discuss clinical developments in targeting these pathways in different disease settings, and introduce VISTA as a putative therapeutic target.


B7 family; co-inhibitory molecules; co-stimulatory molecules

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