Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma.

Published

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

  • 21355078

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-10-0250

Language

  • eng

Conference Location

  • United States