Clinical and Experimental Medicine

, Volume 11, Issue 3, pp 163–170 | Cite as

B7-H4 expression in various tumors determined using a novel developed monoclonal antibody

  • Yun Qian
  • Ling Shen
  • Linfang Cheng
  • Zhigang Wu
  • Hangping YaoEmail author
Original Article


B7-H4, a new member of the B7 family, may participate in the negative regulation of cell-mediated immunity, while aberrant B7-H4 expression is detected in some tumors and it participates in the occurrence and development of the tumors. In this study, we developed one monoclonal antibody (mAb) whose clone No. was 4H8 against the extracellular domains of B7-H4 through immunization of Balb/c mice with the 3T3-mB7-H4 cells that expressed extrinsic B7-H4 stably. And we detected the expression characteristics of B7-H4 in various tumors using 4H8 mAb by enzyme-linked immunosorbent assay (ELISA), immunoprecipitation and immunohistochemistry (IHC) analysis. B7-H4 expression was significantly higher in the tumor tissues derived from uterus, breast, and colon than in their corresponding normal tissues. Further, the B7-H4 expression was related to the stage of the tumors. In contrast, B7-H4 expression did not differ significantly between the tumor tissues derived from the stomach and liver and the normal tissues. Different expression levels of B7-H4 in the tumors indicated that B7-H4 may be involved in tumor formation and development. Specific mAbs against B7-H4 will be useful in studying the role of B7-H4 in tumor pathogenesis and pathological process.


B7-H4 Monoclonal antibody Tumor pathogenesis Immune escape 



This work was supported by a grant (No. 30972777) from the National Natural Science Foundation of China (to HPY). This paper is proofread by a native English professional with science background at Elixigen Corporation.

Conflict of interest

The authors declare that they have no conflict of interest related to the publication of this manuscript.


  1. 1.
    Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L (2003) B7–H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18:849–861PubMedCrossRefGoogle Scholar
  2. 2.
    Chen L (2004) Co-inhibitory molecules of the B7- CD28 family in the control of T cell immunity. Nat Rev Immunol 4:336–347PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz RH (1990) A cell culture mode for T lymphocyte clonal anergy. Science 248:l349–1356CrossRefGoogle Scholar
  4. 4.
    Chambers CA (2001) The expanding world of co-stimulation: the two-signal model revisited. Trends Immunol 22:217–223PubMedCrossRefGoogle Scholar
  5. 5.
    Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS, Zhu Y, Flies DB, Tamada K, Chen L (2003) Genomic organization and expression analysis of B7–H4, an immune inhibitory molecule of the B7 family. J Immunol 171:4650–4654PubMedGoogle Scholar
  6. 6.
    Yigit R, Massuger LF, Figdor CG, Torensma R (2010) Ovarian cancer creates a suppressive microenvironment to escape immune elimination. Gynecol Oncol 117:366–372PubMedCrossRefGoogle Scholar
  7. 7.
    Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK, Wang X (2006) B7–H3 and B7–H4 expression in non-small-cell lung cancer. Lung Cancer 53:143–151PubMedCrossRefGoogle Scholar
  8. 8.
    Salceda S, Tang T, Kmet M, Munteanu A, Ghosh M, Macina R, Liu W, Pilkington G, Papkoff J (2005) The immunomodulatory protein B7–H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res 306:128–141PubMedCrossRefGoogle Scholar
  9. 9.
    Cheng L, Jiang J, Gao R, Wei S, Nan F, Li S, Kong B (2009) B7–H4 expression promotes tumorigenesis in ovarian cancer. Int J Gynecol Cancer 19:1481–1486PubMedCrossRefGoogle Scholar
  10. 10.
    Jiang J, Zhu Y, Wu C, Shen Y, Wei W, Chen L, Zheng X, Sun J, Lu B, Zhang X (2010) Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer. Cancer Immunol Immunother [Epub ahead of print]Google Scholar
  11. 11.
    Qian Y, Yao HP, Cheng LF, Shen L, Gu LJ, Tao L, Zhang LH (2009) Expression and identification of recombinant mouse gene B7–H4. J Zhejiang Univ Med Sci 38:117–124Google Scholar
  12. 12.
    Yao HP, Luo YL, Feng L, Cheng LF, Lu Y, Li W, Wang MH (2006) Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biol Ther 5:1179–1186PubMedCrossRefGoogle Scholar
  13. 13.
    Nelson PN, Reynolds GM, Waldron EE, Ward E, Giannopoulos K, Murray PG (2000) Monoclonal antibodies. Mol Pathol 53:111–117PubMedCrossRefGoogle Scholar
  14. 14.
    Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMedGoogle Scholar
  15. 15.
    Zang XX, Loke P, Kim J, Murphy K, Waitz R, Allison JP (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci USA 100:10388–10392PubMedCrossRefGoogle Scholar
  16. 16.
    Prasad DVR, Richards S, Mai XM, Dong C (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity 18:863–873PubMedCrossRefGoogle Scholar
  17. 17.
    Cheng L, Jiang J, Gao R, Wei S, Nan F, Li S, Kong B (2009) B7–H4 expression promotes tumorigenesis in ovarian cancer. Int J Gynecol Cancer 19:1481–1486PubMedCrossRefGoogle Scholar
  18. 18.
    Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2005) B7–h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 11:1842–1848PubMedCrossRefGoogle Scholar
  19. 19.
    Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2006) B7–H4 overexpression in ovarian tumors. Gynecol Oncol 100:44–52PubMedCrossRefGoogle Scholar
  20. 20.
    Miyatake T, Tringler B, Liu W, Liu SH, Papkoff J, Enomoto T, Torkko KC, Dehn DL, Swisher A, Shroyer KR (2007) B7–H4 (DD-O110) is overexpressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration. Gynecol Oncol 106:119–127PubMedCrossRefGoogle Scholar
  21. 21.
    Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2006) B7–H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Proc Nati Acad Sci USA 103:10391–10396CrossRefGoogle Scholar
  22. 22.
    Awadallah NS, Shroyer KR, Langer DA, Torkko KC, Chen YK, Bentz JS, Papkoff J, Liu W, Nash SR, Shah RJ (2008) Detection of B7–H4 and p53 in pancreatic cancer: potential role as a cytological diagnostic adjunct. Pancreas 36:200–206PubMedCrossRefGoogle Scholar
  23. 23.
    Simon I, Zhuo S, Corral L, Diamandis EP, Sarno MJ, Wolfert RL, Kim NW (2006) B7–H4 Is a novel membrane-bound protein and a candidate serum and tissue biomarker for ovarian cancer. Cancer Res 66:1570–1575PubMedCrossRefGoogle Scholar
  24. 24.
    Dube DH, Bertozzi CR (2005) Glycans in cancer and inflammation-potential for therapeutics and diagnostics. Nat Rev Drug Discov 4:477–488PubMedCrossRefGoogle Scholar
  25. 25.
    Park GB, Song H, Kim YS, Sung M, Ryu JW, Lee HK, Cho DH, Kim D, Lee WJ, Hur DY (2009) Cell cycle arrest induced by engagement of B7–H4 on Epstein-Barr virus-positive B-cell lymphoma cell lines. Immunology 128:360–368PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Yun Qian
    • 1
    • 2
  • Ling Shen
    • 1
  • Linfang Cheng
    • 1
  • Zhigang Wu
    • 1
  • Hangping Yao
    • 1
    Email author
  1. 1.State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Institute of ImmunologyZhejiang UniversityHangzhouChina

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