B7-H3/CD276 Immune Checkpoint Pathway

B7-H3 / CD276 Immune Checkpoint Pathway: Description

B7-H3 / CD276, identified in 2001, is a type I transmembrane protein that shares 20%–27% amino acid identity with other B7 family members.
Initial work on the functional properties of B7-H3 / CD276 showed a stimulatory effect of human B7-H3 / CD276 on T-cells. In vitro, B7-H3 immune checkpoint pathway was able to increase proliferation of both CD4+ and CD8+ T-cells, enhance the induction of cytotoxic T lymphocytes (CTLs), and selectively stimulate interferon-gamma (IFN-γ) production in the presence of anti-CD3 Abs to mimic the TCR signal . B7-H3 / CD276-driven antitumor immunity was mediated by CD8+ T-cells and NK cells. In an orthotopic murine colon cancer model, treatment by intratumoral injection of an adenovirus expressing mouse B7-H3 / CD276 (Ad-B7-H3-GFP) resulted in a reduction of tumor size compared to control animals.
In contrast to these findings,which strongly suggest a stimulatory effect of B7-H3 immune checkpoint pathway on T-cell responses and antitumor immunity, other groups have proposed opposite functions for B7-H3 / CD276. In mice, B7-H3 / CD276 protein inhibited T-cell activation and effector cytokine production. Furthermore, an antagonistic mAb to B7-H3 / CD276 enhanced T-cell proliferation in vitro and led to exacerbated experimental autoimmune encephalomyelitis (EAE) in vivo. Moreover, B7-H3 / CD276–/– mice developed more severe airway inflammation under conditions in which T helper cells differentiated toward Th1 rather than Th2. In a different in vitro study, B7-H3 immune checkpoint pathway inhibited T-cell proliferation of both CD4+ and CD8+ T-cells mediated by Ab to T-cell receptor or allogeneic APCs .

B7-H3 / CD276 Immune Checkpoint Pathway: Reference

Martin Loos et al. B7-H3 and Its Role in Antitumor Immunity. Clinical and Developmental Immunology. 2010.