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

R. Houston Thompson, Haidong M Dong, Eugene D Kwon

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

B7-H1 encompasses a recently discovered cell surface glycoprotein within the B7 family of T-cell coregulatory 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.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume13
Issue number2 II
DOIs
StatePublished - Jan 15 2007

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Carcinoma
Kidney
Renal Cell Carcinoma
Neoplasms
Therapeutics
T-Lymphocytes
Aptitude
Social Adjustment
Membrane Glycoproteins
Nephrectomy
Cellular Immunity
Paraffin
Disease Progression
Immunity
Cell Survival
Necrosis
Survival Rate
Macrophages
Monoclonal Antibodies
Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Implications of B7-H1 expression in clear cell carcinoma of the kidney for prognostication and therapy. / Thompson, R. Houston; Dong, Haidong M; Kwon, Eugene D.

In: Clinical Cancer Research, Vol. 13, No. 2 II, 15.01.2007.

Research output: Contribution to journalArticle

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abstract = "B7-H1 encompasses a recently discovered cell surface glycoprotein within the B7 family of T-cell coregulatory 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.",
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