B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

Amy E. Krambeck, R. Houston Thompson, Haidong Dong, Christine M. Lohse, Eugene S. Park, Susan M. Kuntz, Bradley C. Leibovich, Michael L. Blute, John C. Cheville, Eugene D. Kwon

Research output: Contribution to journalArticle

241 Scopus citations

Abstract

B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.

Original languageEnglish (US)
Pages (from-to)10391-10396
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number27
DOIs
StatePublished - Jul 4 2006

Keywords

  • B7-H1
  • Costimulation
  • Immunotherapy
  • Kidney neoplasms
  • Tumor biomarker

ASJC Scopus subject areas

  • General

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