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Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):709s-715s.

Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy.

Author information

1
Departments of Urology and Immunology, Mayo Medical School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Abstract

B7-H1 encompasses a recently discovered cell surface glycoprotein within the B7 family of T-cell co-regulatory molecules. B7-H1 expression can be induced on activated T lymphocytes and is normally expressed by macrophage lineage cells. In addition, some human tumors acquire the ability to aberrantly express B7-H1. Tumor-associated B7-H1, as well as B7-H1 on activated lymphocytes, has been shown to impair antigen-specific T-cell function and survival in vitro. In contrast, in vivo monoclonal antibody-mediated blockade of B7-H1 has been shown to potentiate antitumoral responses in several murine cancer models. Consequently, tumor-associated B7-H1 has garnered much attention in the recent literature as a potential inhibitor of host antitumoral immunity. Our group has recently reported that B7-H1 is aberrantly expressed in both primary and metastatic renal cell carcinoma (RCC) as revealed via immunohistochemical staining of both fresh-frozen and paraffin-embedded nephrectomy specimens. In addition, we have shown that B7-H1 expression by clear cell RCC tumors (or infiltrating mononuclear cells) correlates with aggressive pathologic features, including advanced tumor-node-metastasis stage, tumor size, higher nuclear grade, and coagulative necrosis. In one study of 306 patients, with a median clinical follow-up of 11 years, we reported that RCC B7-H1 expression correlates with increased risk of disease progression, cancer-specific death, and overall mortality even after multivariate adjustment. Five-year cancer-specific survival rates in this study were 42% and 83% for patients harboring B7-H1(+) versus B7-H1(-) RCC tumors, respectively. Such associations may relate to the recognized ability of B7-H1 to inhibit T-cell-mediated antitumoral immunity. In summary, B7-H1 encompasses a potent independent predictor of prognosis for patients with RCC and an extremely promising target to facilitate immunotherapeutic responses during the management of this treatment-refractory tumor.

PMID:
17255298
DOI:
10.1158/1078-0432.CCR-06-1868
[Indexed for MEDLINE]
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