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Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10391-10396. doi: 10.1073/pnas.0600937103. Epub 2006 Jun 23.

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

Author information

1
Departments of *Urology.
2
Immunology.
3
Health Sciences Research, and.
4
Laboratory Medicine and Pathology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905.
5
Departments of *Urology, kwon.eugene@mayo.edu.

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.

PMID:
16798883
PMCID:
PMC1502468
DOI:
10.1073/pnas.0600937103
[Indexed for MEDLINE]
Free PMC Article

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