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

      Clinical cancer research : an official journal of the American Association for Cancer Research

      Solubility, Adult, Aged, Aged, 80 and over, Amino Acid Sequence, Antigens, CD, blood, immunology, isolation & purification, pharmacology, Antigens, CD274, Apoptosis, drug effects, CD4-Positive T-Lymphocytes, physiology, CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell, metabolism, pathology, Cell Line, Tumor, Culture Media, Conditioned, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunosuppressive Agents, Kidney Neoplasms, Male, Middle Aged, Molecular Sequence Data, Recombinant Proteins

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          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. 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. 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). 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.

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