Significance of B7-H1 overexpression in kidney cancer.
B7-H1 is a cell surface glycoprotein belonging to the B7 family of costimulatory molecules. Constitutive protein expression is restricted to a fraction of macrophage-lineage cells, although B7-H1 can be induced on activated T lymphocytes. In addition, some human tumor cells can acquire the ability to aberrantly express B7-H1. In vitro studies demonstrate that B7-H1, expressed by tumor cells or activated lymphocytes, impairs T-cell function and survival and enhances apoptosis of activated tumor-specific T cells. Consistent with this, in vivo monoclonal antibody blockade of B7-H1 has been shown to potentiate antitumor responses in several murine cancer models. Thus, tumor-associated B7-H1 has recently garnered much attention as a potential inhibitor of host antitumor immunity. We describe herein the published investigations looking at the role of B7-H1 in renal cell carcinoma (RCC). Clinical observations demonstrate that B7-H1 is aberrantly expressed in primary and metastatic RCC. The group from Mayo Clinic recently performed immunohistochemistry on fresh-frozen and paraffin-embedded nephrectomy specimens. All patients had clear-cell RCC, and pathologic evaluation was performed by a single urologic pathologist. Their results demonstrated that B7-H1, expressed by tumor cells or lymphocytes, is associated with aggressive pathologic features, including TNM stage, nuclear grade, tumor size, and coagulative necrosis. With a median clinical follow-up of 11 years, patients with tumor B7-H1 were at significant risk of disease progression, cancer-specific death, and overall mortality even after multivariate analyses. Five-year cancer-specific survival rates were 42% and 83% for patients with and without tumor B7-H1, respectively. The basis for these associations could relate to the recognized ability of B7-H1 to inhibit antitumor T-cell-mediated immunity. Based on the current literature, B7-H1 is an independent predictor of prognosis in RCC and represents a promising target for immune manipulation in this refractory tumor.
Thompson
R Houston
RH
Departments of Urology and Immunology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
Kwon
Eugene D
ED
D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human