Cancer Immunology, Immunotherapy

, Volume 56, Issue 8, pp 1173–1182

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

  • Juro Nakanishi
  • Yoshihiro Wada
  • Koichiro Matsumoto
  • Miyuki Azuma
  • Ken Kikuchi
  • Shoichi Ueda
Original Article

DOI: 10.1007/s00262-006-0266-z

Cite this article as:
Nakanishi, J., Wada, Y., Matsumoto, K. et al. Cancer Immunol Immunother (2007) 56: 1173. doi:10.1007/s00262-006-0266-z

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.

Keywords

B7-H1/PD-L1PD-1CostimulationUrothelial cancerT cellAntitumor immunity

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Juro Nakanishi
    • 1
  • Yoshihiro Wada
    • 1
  • Koichiro Matsumoto
    • 2
  • Miyuki Azuma
    • 3
  • Ken Kikuchi
    • 4
  • Shoichi Ueda
    • 1
  1. 1.Department of Urology, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
  2. 2.Research Institute for Diseases of the Chest, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  3. 3.Department of Molecular Immunology, Graduate SchoolTokyo Medical and Dental UniversityTokyoJapan
  4. 4.Medical Information Technology and Administration PlanningKumamoto University HospitalKumamotoJapan