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Serum-Soluble B7x Is Elevated in Renal Cell Carcinoma Patients and Is Associated with Advanced Stage

¹ Department of Surgery, Urology Service, ² Howard Hughes Medical Institute, Immunology Program, Ludwig Center for Cancer Immunotherapy, ³ Department of Medicine, Genitourinary Oncology Service, and ⁴ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York and Departments of ⁵ Health Sciences Research, ⁶ Pathology, and ⁷ Urology, Mayo Clinic, Rochester, Minnesota

Requests for reprints: James P. Allison, Howard Hughes Medical Institute, Immunology Program, Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. Phone: 646-888-2332; Fax: 646-422-0618; E-mail: allisonj{at}mskcc.org.

Key Words: Carcinoma, renal cell • Tumor markers, biological • T lymphocytes, Lymphocyte activation

B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum-soluble B7x (sB7x) and investigated 101 patients with clear cell RCC who underwent nephrectomy between 2003 and 2007. For controls, we obtained serum from 101 sex-matched blood donors within the same age range. Following an ELISA for sB7x, detectable levels (>0.1 ng/mL) of sB7x were observed in 53 RCC patients compared with 18 controls (P < 0.001). Median (range) concentrations of sB7x for RCC patients and controls were 14.4 ng/mL (0.1–56.9) and 2.7 ng/mL (0.2–37.1), respectively. For RCC patients with detectable sB7x, median levels were significantly higher for patients with a tumor thrombus (19.2 versus 6.6 ng/mL; P = 0.007), positive lymph nodes (41.3 versus 10.3 ng/mL; P = 0.018), and distant metastases at nephrectomy (43.3 versus 8.5 ng/mL; P = 0.002) and tended to be higher in patients with high-grade tumors (18.8 versus 8.5; P = 0.090). Additionally, median sB7x levels for tumor-node-metastasis stage I to IV RCC were 6.6, 10.3, 14.5, and 43.3 ng/mL, respectively (P = 0.012). In this first evaluation of sB7x in RCC, we show that RCC patients are more likely to have detectable sB7x compared with controls and higher sB7x levels correlate with advanced tumor stage. These early results merit further investigation of this serum marker for potential diagnostic and prognostic purposes. [Cancer Res 2008;68(15):6054–8]