Details

Autor(en) / Beteiligte

• Thompson, R. Houston
• Gillett, Michael D.
• Cheville, John C.
• Lohse, Christine M.
• Dong, Haidong
• Webster, W. Scott
• Krejci, Kent G.
• Lobo, John R.
• Sengupta, Shomik
• Chen, Lieping
• Zincke, Horst
• Blute, Michael L.
• Strome, Scott E.
• Leibovich, Bradley C.
• Kwon, Eugene D.
• Allison, James P.

Titel

Costimulatory B7-H1 in Renal Cell Carcinoma Patients: Indicator of Tumor Aggressiveness and Potential Therapeutic Target

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-12, Vol.101 (49), p.17174-17179

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.