title: B7-H4 as a potential target for immunotherapy for gynecologic cancers: a closer look.
abstract: B7-H4 is a transmembrane protein that binds an unknown receptor on activated T cells resulting in inhibition of T-cell effector function via cell cycle arrest, decreased proliferation, and reduced IL-2 production. B7-H4 is up-regulated on the surface of cancer cells and immunosuppressive tumor-associated macrophages (TAMs) in a variety of human cancers. Notably, B7-H4 expression levels inversely correlate with patient survival in ovarian cancer, making B7-H4 an attractive candidate for therapeutic intervention. Here, we summarize the experimental data and methodologies that have revealed B7-H4's mRNA and protein expression and function in both mice and humans since its discovery in 2003, with a specific focus on B7-H4's role in ovarian cancer. We also underscore the discrepancies in published data due to high variability in methodology and use of different antibodies, most of which are not commercially available. Finally, since B7-H4 is expressed on tumor cells and TAMs in various cancer types, directing therapeutics against B7-H4 could have tremendous synergistic outcomes in favorably altering the tumor micro-environment and eliminating cancer cells. We highlight the therapeutic potential of targeting B7-H4, both by comparing other negative immune modulators such as PD-1 and CTLA-4 and by identifying novel methods to target B7-H4 directly or indirectly to overcome B7-H4-mediated T-cell inhibition.
authors.affiliation: Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jenessa B
authors.initials: JB
authors.lastname: Smith
authors.affiliation: Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Stashwick
authors.affiliation: Ovarian Cancer Research Center, Department of Pathology and Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Powell
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
keywords: B7-H4; Ovarian cancer; Targeted therapies