B7 homolog 3 in pancreatic cancer.

ABSTRACT

Despite advances in cancer treatment, pancreatic cancer (PC) remains a disease with high mortality rates and poor survival outcomes. The B7 homolog 3 (B7-H3) checkpoint molecule is overexpressed among many malignant tumors, including PC, with low or absent expression in healthy tissues. By modulating various immunological and nonimmunological molecular mechanisms, B7-H3 may influence the progression of PC. However, the impact of B7-H3 on the survival of patients with PC remains a subject of debate. Still, most available scientific data recognize this molecule as a suppressive factor to antitumor immunity in PC. Furthermore, it has been demonstrated that B7-H3 stimulates the migration, invasion, and metastasis of PC cells, and enhances resistance to chemotherapy. In preclinical models of PC, B7-H3-targeting monoclonal antibodies have exerted profound antitumor effects by increasing natural killer cell-mediated antibody-dependent cellular cytotoxicity and delivering radioisotopes and cytotoxic drugs to the tumor site. Finally, PC treatment with B7-H3-targeting antibody-drug conjugates and chimeric antigen receptor T cells is being tested in clinical studies. This review provides a comprehensive analysis of all PC-related studies in the context of B7-H3 and points to deficiencies in the current data that should be overcome by future research.