title: Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Frigola
authors.forename: Brant A
authors.initials: BA
authors.lastname: Inman
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Krco
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.forename: Bradley
authors.initials: B
authors.lastname: Leibovich
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000097:blood* / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000302:isolation & purification / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins