B7-H1 glycoprotein blockade: A novel strategy to enhance immunotherapy in patients with renal cell carcinoma

Cancer cell expression of the B7-H1 glycoprotein has been implicated as a potent inhibitor of T cell–mediated antitumoral immunity. We recently reported that B7-H1 is aberrantly expressed in renal cell carcinoma (RCC) and suggested that blockade of B7-H1, as demonstrated in several murine cancer mod...

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Veröffentlicht in:Urology (Ridgewood, N.J.) N.J.), 2005-11, Vol.66 (5), p.10-14
Hauptverfasser: Thompson, R. Houston, Webster, W. Scott, Cheville, John C., Lohse, Christine M., Dong, Haidong, Leibovich, Bradley C., Kuntz, Susan M., Sengupta, Shomik, Kwon, Eugene D., Blute, Michael L.
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Sprache:eng
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Zusammenfassung:Cancer cell expression of the B7-H1 glycoprotein has been implicated as a potent inhibitor of T cell–mediated antitumoral immunity. We recently reported that B7-H1 is aberrantly expressed in renal cell carcinoma (RCC) and suggested that blockade of B7-H1, as demonstrated in several murine cancer models, represents a promising therapeutic target in RCC. Herein, we update our results with tumor-associated B7-H1 and discuss future clinical applications. Between 2000 and 2002, 196 patients underwent nephrectomy for clear-cell RCC and had fresh-frozen tissue available for review. Immunohistochemical analysis was performed on tumor cryosections, and outcome was obtained from the Mayo Clinic Nephrectomy Registry (Rochester, MN). At last follow-up 38 of the 196 patients died of RCC. The median duration of follow-up for patients still alive was 2.7 years. Among the 196 RCC specimens, 130 (66.3%) demonstrated aberrant tumor-associated B7-H1 expression. Patients with tumor-associated B7-H1 expression were significantly more likely to die of RCC compared with patients whose specimens did not have aberrant tumor-associated B7-H1 expression (risk ratio, 3.34; 95% confidence interval [CI], 1.30 – 8.55; P = 0.012). This risk persisted in multivariate analysis even after adjusting for the Mayo Clinic SSIGN (stage, size, grade, and necrosis) score (risk ratio, 3.52; 95% CI, 1.35–9.15; P = 0.010). Tumor-associated B7-H1 expression is significantly associated with poor prognosis among patients with clear-cell RCC. Manipulation of B7-H1 with therapeutic intent remains a realistic and viable therapeutic option.
ISSN:0090-4295
1527-9995
DOI:10.1016/j.urology.2005.06.010