title: Potential targeting of B7-H4 for the treatment of cancer.
abstract: Observations noting the presence of white blood cell infiltrates within tumors date back more than a century, however the cellular and molecular mechanisms regulating tumor immunity continue to be elucidated. The recent successful use of monoclonal antibodies to block immune regulatory pathways to enhance tumor-specific immune responses for the treatment of cancer has encouraged the identification of additional immune regulatory receptor/ligand pathways. Over the past several years, a growing body of data has identified B7-H4 (VTCN1/B7x/B7S1) as a potential therapeutic target for the treatment of cancer. The potential clinical significance of B7-H4 is supported by the high levels of B7-H4 expression found in numerous tumor tissues and correlation of the level of expression on tumor cells with adverse clinical and pathologic features, including tumor aggressiveness. The biological activity of B7-H4 has been associated with decreased inflammatory CD4+T-cell responses and a correlation between B7-H4-expressing tumor-associated macrophages and FoxP3+regulatory T cells (Tregs) within the tumor microenvironment. Since B7-H4 is expressed on tumor cells and tumor-associated macrophages in various cancer types, therapeutic blockade of B7-H4 could favorably alter the tumor microenvironment allowing for antigen-specific clearance tumor cells. The present review highlights the therapeutic potential of targeting B7-H4.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Joseph R
authors.identifier: 0000-0002-5818-8515
authors.initials: JR
authors.lastname: Podojil
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008264:Macrophages / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019139:Tumor Escape; D059016:Tumor Microenvironment; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human
keywords: B7-H4; B7-H4 receptor; CD4+ T cell; cancer; co-stimulatory/co-inhibitory molecule; regulatory T cell