Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy.
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.
Thompson
R Houston
RH
Departments of Urology and Immunology, Mayo Medical School, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Dong
Haidong
H
Kwon
Eugene D
ED
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000378:metabolism; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis; D011379:Prognosis; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D060890:B7-H1 Antigen; C423236:CD274 protein, human