B7-H1 is correlated with malignancy-grade gliomas but is not expressed exclusively on tumor stem-like cells

Neuro Oncol. 2009 Dec;11(6):757-66. doi: 10.1215/15228517-2009-014.


Human glioblastoma is well known for its capacity to interfere with effective antitumor immune responses. B7-H1 is the third member of the B7 family that plays important roles in tumor immune evasion. Recent studies have shown that brain tumor stem-like cells (TSCs) contribute to tumorigenesis and radioresistance. However, the relationship between B7-H1 and the clinical behavior of brain TSCs remains unclear. In the present study, we report that B7-H1 is correlated with the malignancy grade of astrocyte tumors. B7-H1 was significantly upregulated at the growing edge of the tumors. Immunostaining and flow cytometric analysis indicate that B7-H1 was expressed primarily by Ki67-negative tumor cells. In vitro, tumors cultured under medium favoring the growth of neural stem cells were able to form spheres, along with expression of neural stem/progenitor cell markers. These cells were able to differentiate into different neural lineages when cultured in differentiation medium, indicating that these cells have TSC characteristics. We also found that B7-H1 was expressed, but not exclusively on CD133-positive stem cells. Interestingly, we found that CD133-negative tumor cells also had the capacity to form brain tumors. Our data establish a correlation between the expression of the negative costimulatory molecule B7-H1 and the malignancy grade of human gliomas, suggesting that B7-H1 may be a novel tumor marker and target for therapy, although it is not expressed exclusively on brain TSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / metabolism*
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • B7-H1 Antigen
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Glycoproteins / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Interferon-gamma / metabolism
  • Ki-67 Antigen / metabolism
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Peptides / metabolism
  • Prognosis
  • Xenograft Model Antitumor Assays


  • AC133 Antigen
  • Antigens, CD
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Glycoproteins
  • Ki-67 Antigen
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Interferon-gamma