B7-H3 immunoregulatory roles in cancer

B7 homolog 3 (B7-H3, also called CD276) is a checkpoint of B7 family that is aberrantly and consistently expressed in several human cancers, and its overexpression correlates with weak prognosis. B7-H3 is expressed on a number of cells, and it acts as a driver of immune evasion. This is mediated through hampering T cell infiltration and promoting exhaustion of CD8+ T cells. Increased B7-H3 activity also promotes macrophage polarity toward pro-tumor type 2 (M2) phenotype. In addition, high B7-H3 activity induces aberrant angio-genesis to promote hypoxia, a result of which is resistance to common immune checkpoint inhibitor (ICI) therapy. This is mediated through the impact of hypoxia on dampening CD8+ T cell recruitment into tumor area. The immunosuppressive property of B7-H3 offers insights into targeting this checkpoint as a desired approach in cancer immunotherapy. B7-H3 can be a target in blocking monoclonal antibodies (mAbs), combination therapies, chimeric antigen receptor-modified T (CAR-T) cells and bispecific antibodies.

Automated summary

B7-H3 is a checkpoint that is overexpressed in several human cancers and associated with poor prognosis. It drives immune evasion by impairing T cell infiltration and promoting CD8+ T cell exhaustion. High B7-H3 activity also induces pro-tumor macrophage polarization and aberrant angiogenesis, leading to resistance to immune checkpoint inhibitor therapy. Targeting B7-H3 in cancer immunotherapy holds promise as a desired approach.