Costimulatory molecule B7‐H1 in primary and metastatic clear cell renal cell carcinoma

Abstract

BACKGROUND Cancer cell expression of costimulatory molecule B7‐H1 has been implicated as a potent inhibitor of T‐cell–mediated antitumoral immunity. The authors recently reported that B7‐H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7‐H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7‐H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow‐up and investigated the potential role of B7‐H1 in metastatic RCC. METHODS Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7‐H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7‐H1–positive tumor cells and lymphocytes. RESULTS Variable levels of B7‐H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor‐infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7‐H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7‐H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97–8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23–5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7‐H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7‐H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS Patients with RCC with high B7‐H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7‐H1. The authors surmised that B7‐H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy. Cancer 2005. © 2005 American Cancer Society.