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

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

Juro Nakanishi et al. Cancer Immunol Immunother. 2007 Aug.

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.

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Figures

Fig. 1

Fig. 1

Immunohistostaining with anti-B7-H1 mAb in urothelial cancer sections. Representative cases from WHO grade 3 with high B7-H1 expression (a), and grade 3 with low B7-H1 expression (b) tumors are shown. Bars 60 μm

Fig. 2

Fig. 2

Association between the primary tumor (T) classification and B7-H1 expression in tumor cells, and the ratio of TILs. Tumor-associated B7-H1 expression is significantly associated with T classification (P = 0.031). The association between TILs and T classification had a tendency toward an inverse association, although the difference was not statistically significant (P = 0.084)

Fig. 3

Fig. 3

A majority of TILs, including both CD4+ and CD8+ T cells, expressed PD-1 at high levels. On CD4+ TILs from tumor specimens 5, 6, and 11, the percentages of PD-1 expression were 77.50, 90.73, and 84.10%, respectively. On CD8+ TILs from tumor specimens 5, 6, and 11, the percentages of PD-1 expression were 95.17, 95.13, and 78.52%, respectively (broken line, stained with control mAb; regular line, stained with antibody against PD-1)

Fig. 4

Fig. 4

Overall (a) and cause-specific (b) survival in 65 patients with urothelial cancer in relation to tumor B7-H1 status. The patients with high B7-H1 expression had a poorer prognosis than those with low B7-H1 expression (a P = 0.021 and b P = 0.041). c Recurrence-free survival in 62 patients who had no visible rest of tumor after surgery in relation to tumor B7-H1 status. The patients with high B7-H1 expression had a poorer prognosis than those with low B7-H1 expression (P = 0.026). P values were determined by the log-rank test

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