Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma.
Journal Article (Journal Article)
PURPOSE: Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome. EXPERIMENTAL DESIGN: We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome. RESULTS: sB7-H1 was detected in the cell supernatants of some B7-H1-positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P < 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010). CONCLUSION: Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome.
Full Text
Duke Authors
Cited Authors
- Frigola, X; Inman, BA; Lohse, CM; Krco, CJ; Cheville, JC; Thompson, RH; Leibovich, B; Blute, ML; Dong, H; Kwon, ED
Published Date
- April 1, 2011
Published In
Volume / Issue
- 17 / 7
Start / End Page
- 1915 - 1923
PubMed ID
- 21355078
Pubmed Central ID
- PMC3241002
Electronic International Standard Serial Number (EISSN)
- 1557-3265
Digital Object Identifier (DOI)
- 10.1158/1078-0432.CCR-10-0250
Language
- eng
Conference Location
- United States