Living reference work entry


B7-H4, also known as B7x or B7S1, is a new member of the B7 family of immune co-signaling molecules. Despite the wide distribution in mRNA levels, B7-H4 protein expression is generally absent in peripheral tissues but is increased on many cancer cells or tumor-associated immune cells. In addition, B7-H4 up-regulation has shown to be associated with diseases progression and/or outcome in some cancers. The unique expression of B7-H4 in the tumor microenvironment and its potential immune inhibitory functions on both innate and adaptive immune responses represents a novel target for the next-generation cancer diagnosis and immunotherapy.


B7 homolog 4 (B7-H4) Antigen-dependent induction Downstream gene target of p70S6K ELISA Immunohistochemistry Cancer Marker for pancreatic ductal adenocarcinoma (PDA) Neutrophil progenitor cell proliferation Preclinical studies Shield for immunosurveillance evasion Soluble form Staining in tumor endothelial vasculature T-cell inhibition T regulatory cell trafficking Therapeutics for autoimmune diseases and islet transplantation B7S11–3. See B7 homolog 4 (B7-H4) B7x. See B7 homolog 4 (B7-H4) 


  1. Awadallah NS, et al. Detection of B7-H4 and p53 in pancreatic cancer: potential role as a cytological diagnostic adjunct. Pancreas. 2008;36:200–6.CrossRefPubMedGoogle Scholar
  2. Azuma T, et al. Potential role of decoy B7-H4 in the pathogenesis of rheumatoid arthritis: a mouse model informed by clinical data. PLoS Med. 2009;6, e1000166.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cao Q et al. IL-10/TGF-{beta}-modified macrophages induce regulatory T cells and protect against adriamycin nephrosis. J Am Soc Nephrol. 2010;21:933–42.Google Scholar
  4. Choi IH, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol. 2003;171:4650–4.CrossRefPubMedGoogle Scholar
  5. Crispen PL, Boorjian SA, Lohse CM, Leibovich BC, Kwon ED. Predicting disease progression after nephrectomy for localized renal cell carcinoma: the utility of prognostic models and molecular biomarkers. Cancer. 2008;113:450–60.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Heinonen H, et al. Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer. BMC Genomics. 2008;9:348.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Krambeck AE, et al. B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Proc Natl Acad Sci U S A. 2006;103:10391–6.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kryczek I, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med. 2006a;203:871–81.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Kryczek I, et al. Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J Immunol. 2006b;177:40–4.CrossRefPubMedGoogle Scholar
  10. Kryczek I, et al. Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res. 2007;67:8900–5.CrossRefPubMedGoogle Scholar
  11. Park GB, et al. Cell cycle arrest induced by engagement of B7-H4 on Epstein-Barr virus-positive B-cell lymphoma cell lines. Immunology. 2009;128:360–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Prasad DV, Richards S, Mai XM, Dong C. B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity. 2003;18:863–73.CrossRefPubMedGoogle Scholar
  13. Salceda S, et al. The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res. 2005;306:128–41.CrossRefPubMedGoogle Scholar
  14. Shvets A, et al. Impaired negative regulation of homeostatically proliferating T cells. Blood. 2009;113:622–5.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Sica GL, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18:849–61.CrossRefPubMedGoogle Scholar
  16. Simon I, et al. B7-h4 is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Cancer Res. 2006;66:1570–5.CrossRefPubMedGoogle Scholar
  17. Suh WK, et al. Generation and characterization of B7-H4/B7S1/B7x-deficient mice. Mol Cell Biol. 2006;26:6403–11.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Sun Y, et al. B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer. 2006;53:143–51.CrossRefPubMedGoogle Scholar
  19. Thompson RH, et al. Serum-soluble B7x is elevated in renal cell carcinoma patients and is associated with advanced stage. Cancer Res. 2008;68:6054–8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Tringler B, et al. B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res. 2005;11:1842–8.CrossRefPubMedGoogle Scholar
  21. Xu JF et al. Ectopic B7-H4-Ig expression attenuates concanavalin A-induced hepatic injury. Clin Immunol. 2010;136:30–41.Google Scholar
  22. Xue Q, et al. The negative co-signaling molecule b7-h4 is expressed by human bone marrow-derived mesenchymal stem cells and mediates its T-cell modulatory activity. Stem Cells Dev. 2010;19:27–38.Google Scholar
  23. Yao Y, et al. B7-H4 is preferentially expressed in non-dividing brain tumor cells and in a subset of brain tumor stem-like cells. J Neurooncol. 2008;89:121–9.CrossRefPubMedGoogle Scholar
  24. Yee EU, Zaino RJ, Torkko KC, Shroyer KR. B7-H4 expression in Brenner tumours, a descriptive and comparative study. Histopathology. 2010;56:652–4.Google Scholar
  25. Yi KH, Chen L. Fine tuning the immune response through B7-H3 and B7-H4. Immunol Rev. 2009;229:145–51.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Yuan CL, et al. B7-H4 transfection prolongs beta-cell graft survival. Transpl Immunol. 2009;21:143–9.CrossRefPubMedGoogle Scholar
  27. Zang X, et al. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A. 2003;100:10388–92.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Zang X, et al. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci U S A. 2007;104:19458–63.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Zhang J, et al. B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population. BMC Cancer. 2009;9:394.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Zhu G, et al. B7-H4-deficient mice display augmented neutrophil-mediated innate immunity. Blood. 2009;113:1759–67.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Immunobiology and Yale Cancer CenterYale University School of MedicineNew HavenUSA
  2. 2.Cancer Immunology ProgramYale University School of Medicine, Yale Cancer CenterNew HavenUSA

Personalised recommendations