Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target

• DOI: 10.1073/pnas.0406351101
• Publication Date: 2004-11-30T01:25:45Z
• Authors: R. Houston Thompson; Michael D. Gillett; John C. Cheville; Christine M. Lohse; Haidong Dong; W. Scott Webster; Kent G. Krejci; John R. Lobo; Shomik Sengupta; Lieping Chen; Horst Zincke; Michael L. Blute; Scott E. Strome; Bradley C. Leibovich; Eugene D. Kwon
• Keywords: Membrane Glycoproteins; Immunity; Prognosis; Immunohistochemistry; Survival Analysis; B7-H1 Antigen; Neoplasm Proteins; 3. Good health; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; 0302 clinical medicine; Antigens, CD; B7-1 Antigen; Odds Ratio; Humans; Peptides; Carcinoma, Renal Cell; Follow-Up Studies

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.