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, cholangiocarcinoma, breast cancer and endometrial cancer, making B7-H4 an attractive candidate for therapeutic intervention.