Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers

Cancer Immunol Immunother. 2007 Aug;56(8):1173-82. doi: 10.1007/s00262-006-0266-z. Epub 2006 Dec 22.

Abstract

Purpose: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis.

Experimental design: Sixty-five urothelial cancer cases were examined. B7-H1 expression in tumors and the numbers and phenotypes of tumor-infiltrating lymphocytes were evaluated by immunohistochemistry and flow cytometry.

Results: A substantial expression of B7-H1 was observed in all urothelial cancers investigated. Tumor specimens from patients with higher WHO grade or primary tumor classifications showed significantly higher percentages of tumor-associated B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high frequency of postoperative recurrence and poor survival rate. Furthermore, multivariate analysis indicated that tumor-associated B7-H1 was more significant prognostic factor than WHO grade.

Conclusions: Our results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a beneficial target for immunotherapy in human urothelial cancer.

MeSH terms

  • Antigens, CD / analysis*
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • B7-H1 Antigen
  • Carcinoma, Transitional Cell / chemistry*
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / surgery
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunophenotyping
  • Kidney Neoplasms / chemistry
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Kidney Pelvis / chemistry
  • Kidney Pelvis / pathology
  • Kidney Pelvis / surgery
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplasm Recurrence, Local
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis
  • Ureteral Neoplasms / chemistry
  • Ureteral Neoplasms / mortality
  • Ureteral Neoplasms / pathology
  • Ureteral Neoplasms / surgery
  • Urinary Bladder Neoplasms / chemistry*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • Neoplasm Proteins