B7x is an immune checkpoint molecule which belongs to the B7 family of ligands which includes PD-L1, PD-L2, B7-H3 and HHLA2. B7x belongs to the Immunoglobulin superfamily and its protein structure is similar to other members with a N terminus peptide, IgV and IgC like extracellular domain with four cysteine residues. Its receptor is yet to be identified. B7x inhibits T cell proliferation and expansion by IL-2 dependent and non-IL-2 dependent pathways. Even though high levels of B7x mRNA can be detected in most tissues its protein expression is highly limited suggesting significant post translational control. In vivo data, show that B7x plays an important role in limiting autoimmunity in the peripheral tissues and fine-tuning autoimmune responses. B7x is highly expressed in various cancers and in prostate cancer its expression is corelated with poorer outcomes. Local production of IL-6 and IL-10 in various cancers promotes B7x expression and tumor immune evasion. B7x is especially expressed in PD-L1 negative tumors suggesting that this may be an important method of immune evasion in these tumors. Currently drug development, targeting B7x through various mechanisms including monoclonal antibodies and antibody drug conjugates are in development in cancers and increasing B7x expression with fusion proteins in autoimmune diseases is underway.
Keywords: B7 homolog 4; B7-H4; B7S1; B7x; VTCN1; immune checkpoint blockade; immunotherapy; novel immune checkpoints.