Identification of a Soluble Form of B7-H1 That Retains Immunosuppressive Activity and is Associated with Aggressive Renal Cell Carcinoma

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Mar 1

PMID 21355078

Citations 196

Authors

Xavier Frigola

Brant A Inman

Christine M Lohse

Christopher J Krco

John C Cheville

R Houston Thompson

Bradley Leibovich

Michael L Blute

Haidong Dong

Eugene D Kwon

Affiliations

Soon will be listed here.

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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