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

R. Houston Thompson, W. Scott Webster, John C. Cheville, Christine M. Lohse, Haidong M Dong, Bradley C. Leibovich, Susan M. Kuntz, Shomik Sengupta, Eugene D Kwon, Michael L. Blute

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)10-14
Number of pages5
JournalUrology
Volume66
Issue number5 SUPPL.
DOIs
StatePublished - Nov 2005

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Renal Cell Carcinoma
Immunotherapy
Glycoproteins
Neoplasms
Nephrectomy
Odds Ratio
Confidence Intervals
Cellular Immunity
Registries
Necrosis
Therapeutics
Multivariate Analysis
T-Lymphocytes

ASJC Scopus subject areas

  • Urology

Cite this

Thompson, R. H., Webster, W. S., Cheville, J. C., Lohse, C. M., Dong, H. M., Leibovich, B. C., ... Blute, M. L. (2005). B7-H1 glycoprotein blockade: A novel strategy to enhance immunotherapy in patients with renal cell carcinoma. Urology, 66(5 SUPPL.), 10-14. https://doi.org/10.1016/j.urology.2005.06.010

B7-H1 glycoprotein blockade : A novel strategy to enhance immunotherapy in patients with renal cell carcinoma. / Thompson, R. Houston; Webster, W. Scott; Cheville, John C.; Lohse, Christine M.; Dong, Haidong M; Leibovich, Bradley C.; Kuntz, Susan M.; Sengupta, Shomik; Kwon, Eugene D; Blute, Michael L.

In: Urology, Vol. 66, No. 5 SUPPL., 11.2005, p. 10-14.

Research output: Contribution to journalArticle

Thompson, RH, Webster, WS, Cheville, JC, Lohse, CM, Dong, HM, Leibovich, BC, Kuntz, SM, Sengupta, S, Kwon, ED & Blute, ML 2005, 'B7-H1 glycoprotein blockade: A novel strategy to enhance immunotherapy in patients with renal cell carcinoma', Urology, vol. 66, no. 5 SUPPL., pp. 10-14. https://doi.org/10.1016/j.urology.2005.06.010
Thompson, R. Houston ; Webster, W. Scott ; Cheville, John C. ; Lohse, Christine M. ; Dong, Haidong M ; Leibovich, Bradley C. ; Kuntz, Susan M. ; Sengupta, Shomik ; Kwon, Eugene D ; Blute, Michael L. / B7-H1 glycoprotein blockade : A novel strategy to enhance immunotherapy in patients with renal cell carcinoma. In: Urology. 2005 ; Vol. 66, No. 5 SUPPL. pp. 10-14.
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AU - Thompson, R. Houston

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AU - Cheville, John C.

AU - Lohse, Christine M.

AU - Dong, Haidong M

AU - Leibovich, Bradley C.

AU - Kuntz, Susan M.

AU - Sengupta, Shomik

AU - Kwon, Eugene D

AU - Blute, Michael L.

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AB - 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.

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