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


METHODS
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.
Nakanishi
Juro
J
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
Wada
Yoshihiro
Y
Matsumoto
Koichiro
K
Azuma
Miyuki
M
Kikuchi
Ken
K
Ueda
Shoichi
S
D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D060890:B7-H1 Antigen; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000601:surgery; D007682:Kidney Pelvis / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014516:Ureteral Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins