B7-h3

B7-H3 (CD276) is an immune checkpoint molecule and belongs to the anti-inflammatory immune checkpoints (ICs). CD276 is expressed by some solid tumors and is an important key protein for an anticarcinogenic therapy (e.g. by MGA271).

Anti-inflammatory immune checkpoints inhibit the immune reactivity of T lymphocytes, in contrast to pro-inflammatory ICs, which increase the immune reactivity of T lymphocytes. The immune checkpoints are activated by precisely fitting cytokines (ligands) that are presented and released by other cells, e.g. as in B7-H3 by some solid tumor cells.

B7-H3 is a central member of the B7/CD8 family. The B7 family (B7 superfamily) currently consists of 7 members: B7.1 (CD80), B7.2 (CD86), ICOS-L (inducible costimulator ligand), PD-L1 (programmed death-1 ligand), PD-L2 (programmed death-2 ligand), B7-H3 and B7-H4.

The importance of the B7 members lies in the balancing of autoimmunological inflammatory and tumor processes. All B7 members are structurally related, cell membrane-bound protein ligands that bind to receptors of lymphocytes and costimulatively downregulate the immune response. This happens e.g. by an early suppression of IL-2 and can also be reversed by exogenously supplied IL-2.

1. Leitner J et al (2009) B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction. Eur J Immunol 39:1754-1764.
2. Hwang JY et al. (2018) Olive flounder CD276 (B7-H3) a coinhibitory molecule for T cells: Responses during viral hemorrhagic septicemia virus (VHSV) stimulation. Fish Shellfish Immunol 73:228-233.
3. Yonesaka K et al (2018) B7-H3 negatively modulates CTL-mediated cancer immunity. Clin Cancer Res. pii: clincanres.2852.2017.