The B7-H1/PD-1 pathway in cancers associated with infections and inflammation: opportunities for therapeutic intervention

Almost one fifth of malignancies worldwide and about one quarter in China are associated with viral or bacterial infections, mediating an inflammatory environment in the tumor. Hepatitis viruses (B and C), Epstein Barr Virus (EBV), and helicobacter pylori have been linked to liver, gastric, and nasopharyngeal cancer. The context of infection and chronic inflammation in these cancers may provide an opportunity for therapeutic intervention based on the role of immune checkpoint pathways, which are an important defense mechanism of many cancers against a tumor-directed immune response. Specifically, the expression of the inhibitory receptor PD-1 on the surface of activated T cells has been associated with T cell exhaustion in inflammatory and tumor environments. Furthermore, tumors have been found to over-express the PD-1 ligand B7-H1. Recent therapeutic successes with monoclonal antibodies directed against both B7-H1 and PD-1 in patients with advanced melanoma, renal cell cancer (RCC), and non-small cell cancer, along with the prominent role of this immune checkpoint axis in the inflammatory tumor context, suggest that B7-H1/PD-1 blockade may be particularly beneficial in cancers associated with infections and inflammation.