Tumor Biology

, Volume 35, Issue 1, pp 55–60 | Cite as

T-cell infiltration and expressions of T lymphocyte co-inhibitory B7-H1 and B7-H4 molecules among colorectal cancer patients in northeast China’s Heilongjiang province

  • Ming Liang
  • Jingyuan Li
  • Dandan Wang
  • Shuchen Li
  • Yi Sun
  • Tiewei Sun
  • Jing Zhang
  • Xiaoning Chen
  • Qiang Li
  • Shibo Sun
Research Article


Colorectal cancer has an extremely poor prognosis due to its high rate of recurrence and metastasis. The present study aimed to investigate the correlations between the B7-H1 and B7-H4 expressions as well as the clinicopathological characteristics and the prognosis of patients with colorectal cancer. We further inferred from these findings whether T lymphocyte co-inhibitory molecules (B7-H1 and B7-H4) led to a poor prognosis in Heilongjiang patients with colorectal cancer. Survival analysis revealed that the poor prognosis of these patients was unrelated to patient age, tumor size or histological grade, or lymph node metastasis, but was associated with TNM stage, high B7-H1 and B7-H4 expression levels. High B7-H1 and B7-H4 expressions were closely correlated with poor prognosis in patients with colorectal cancer. We speculate that the joint detection of these molecules may clinically apply for diagnosing and predicting poor prognosis of patients with colorectal cancer in northeast China’s Heilongjiang province. In addition, intervention of B7-H1 and B7-H4 may be beneficial for enhancement of immunity in these patients.


Colorectal cancer B7-H1 B7-H4 Prognosis 



We thank for the support by Colleges and Universities in Heilongjiang Province Key Laboratory of Neurobiology topics (Liang Ming; 2013HLJKLNT-09); Heilongjiang Provincial Department of Education Science and Technology Research Project (12531296).

Conflicts of interest



  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2013;63:11–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Faber TJ, Japink D, Leers MP, Sosef MN, von Meyenfeldt MF, Nap M. Activated macrophages containing tumor marker in colon carcinoma: immunohistochemical proof of a concept. Tumor Biol. 2012;33:435–41.CrossRefGoogle Scholar
  3. 3.
    Qing H, Gong W, Che Y, Wang X, Peng L, Liang Y, et al. PAK1-dependent MAPK pathway activation is required for colorectal cancer cell proliferation. Tumor Biol. 2012;33:985–94.CrossRefGoogle Scholar
  4. 4.
    Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013;19:3165–75.PubMedCrossRefGoogle Scholar
  5. 5.
    Lu B, Chen L, Liu L, Zhu Y, Wu C, Jiang J, et al. T-cell-mediated tumor immune surveillance and expression of B7 co-inhibitory molecules in cancers of the upper gastrointestinal tract. Immunol Res. 2011;50:269–75.PubMedCrossRefGoogle Scholar
  6. 6.
    Sica GL, Choi IH, Zhu G, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18:849–61.PubMedCrossRefGoogle Scholar
  7. 7.
    Konishi J, Yamazaki K, Azuma M, et al. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res. 2004;10:5094–100.PubMedCrossRefGoogle Scholar
  8. 8.
    Kryczek I, Wei S, Zhu G, et al. Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res. 2007;67:8900–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Miyatake T, Tringler B, Liu W, et al. B7-H4(DD-O1l0) is over-expressed in high risk uterine endometrioid adenocarcinomas and inversely correlated with tumor T-cell infiltration. Gynecol Oncol. 2007;106:119–27.PubMedCrossRefGoogle Scholar
  10. 10.
    Carreno BM, Collins M. BTLA: a new inhibitory receptor with a B7-like ligand. Trends Immunol. 2003;24:524–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T cell immunity. Nature Rev immunol. 2004;4:336–47.CrossRefGoogle Scholar
  12. 12.
    Choi IH, Zhu G, Siea GL, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol. 2003;171:4650–4.PubMedGoogle Scholar
  13. 13.
    Song H, Li C, Li R, Geng J. Prognostic significance of AEG-1 expression in colorectal carcinoma. Int J Colorectal Dis. 2010;25:1201–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19:813–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, et al. B7-H4 overexpression in ovarian tumors. Gynecol Oncol. 2006;100:44–52.PubMedCrossRefGoogle Scholar
  16. 16.
    Salceda S, Tang T, Kmet M, 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013;19:1021–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Krambeck AE, Thompson RH, Dong H, 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.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Kondratiev S, Sabo E, Yakirevich E, Lavie O, Resnick MB. Intratumoral CD8+ T lymphocytes as a prognostic factor of survival in endometrial carcinoma. Clin Cancer Res. 2004;10:4450–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Matsuda M, Petersson M, Lenkei R, Taupin JL, Magnusson I, Mellstedt H, et al. Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer. 1995;61:765–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Hamanishi J, Mandai M, Iwasaki M, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104:3360–5.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Mugler KC, Singh M, Tringler B, et al. B7–H4 expression in arrange of breast pathology: correlation with tumor T-cell infiltration. Appl Immunohistochem Mol Morphol. 2007;15:363–70.PubMedCrossRefGoogle Scholar
  23. 23.
    Ohno S, Inagawa H, Dhar DK, et al. The degree of macrophage infiltration in the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anti-Cancer Res. 2003;23:5015–22.Google Scholar
  24. 24.
    Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4:71–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med. 2006;203:871–81.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Schoppmann SF, Birner P, Stockl J, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 2002;163:947–56.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Ming Liang
    • 1
    • 4
  • Jingyuan Li
    • 1
  • Dandan Wang
    • 2
  • Shuchen Li
    • 1
  • Yi Sun
    • 3
  • Tiewei Sun
    • 3
  • Jing Zhang
    • 3
  • Xiaoning Chen
    • 3
  • Qiang Li
    • 3
  • Shibo Sun
    • 3
  1. 1.Department of Infectious DiseasesThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Wu Lian De Memorial HospitalThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of SurgeryThe Second Affiliated Hospital of Harbin Medical UniversityHarbinChina
  4. 4.Department of Neurobiology, Harbin Medical University Provincial Key Lab of NeurobiologyHarbin Medical UniversityHarbinChina

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