Potential targeting of B7‐H4 for the treatment of cancer

Summary 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 ( VTCN 1/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 CD 4 + 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.