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 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.
Thompson
R Houston
RH
Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, Minnesota 55905, USA.
Webster
W Scott
WS
Cheville
John C
JC
Lohse
Christine M
CM
Dong
Haidong
H
Leibovich
Bradley C
BC
Kuntz
Susan M
SM
Sengupta
Shomik
S
Kwon
Eugene D
ED
Blute
Michael L
ML
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000037:antagonists & inhibitors*
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008562:Membrane Glycoproteins; D010455:Peptides