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

Xavier Frigola, Brant A. Inman, Christine M. Lohse, Christopher J. Krco, John C. Cheville, R. Houston Thompson, Bradley Leibovich, Michael L. Blute, Haidong M Dong, Eugene D Kwon

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1915-1923
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number7
DOIs
StatePublished - Apr 1 2011

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Immunosuppressive Agents
Renal Cell Carcinoma
Neoplasms
Tumor Cell Line
T-Lymphocytes
Foster Home Care
Protein Sequence Analysis
Serum
Immunity
Proteins
Research Design
Necrosis
Enzyme-Linked Immunosorbent Assay
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. / Frigola, Xavier; Inman, Brant A.; Lohse, Christine M.; Krco, Christopher J.; Cheville, John C.; Thompson, R. Houston; Leibovich, Bradley; Blute, Michael L.; Dong, Haidong M; Kwon, Eugene D.

In: Clinical Cancer Research, Vol. 17, No. 7, 01.04.2011, p. 1915-1923.

Research output: Contribution to journalArticle

Frigola, Xavier ; Inman, Brant A. ; Lohse, Christine M. ; Krco, Christopher J. ; Cheville, John C. ; Thompson, R. Houston ; Leibovich, Bradley ; Blute, Michael L. ; Dong, Haidong M ; Kwon, Eugene D. / Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 7. pp. 1915-1923.
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abstract = "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.",
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AU - Frigola, Xavier

AU - Inman, Brant A.

AU - Lohse, Christine M.

AU - Krco, Christopher J.

AU - Cheville, John C.

AU - Thompson, R. Houston

AU - Leibovich, Bradley

AU - Blute, Michael L.

AU - Dong, Haidong M

AU - Kwon, Eugene D

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AB - 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.

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