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

Amy E. Krambeck, R. Houston Thompson, Haidong M 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

225 Citations (Scopus)

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

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Renal Cell Carcinoma
Survival
Neoplasms
Staining and Labeling
Nephrectomy
Cellular Immunity
Necrosis
Odds Ratio
Lymphocytes
Confidence Intervals
Ligands
T-Lymphocytes
Kidney

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

B7-H4 expression in renal cell carcinoma and tumor vasculature : Associations with cancer progression and survival. / Krambeck, Amy E.; Thompson, R. Houston; Dong, Haidong M; Lohse, Christine M.; Park, Eugene S.; Kuntz, Susan M.; Leibovich, Bradley C.; Blute, Michael L.; Cheville, John C.; Kwon, Eugene D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 27, 04.07.2006, p. 10391-10396.

Research output: Contribution to journalArticle

Krambeck, Amy E. ; Thompson, R. Houston ; Dong, Haidong M ; Lohse, Christine M. ; Park, Eugene S. ; Kuntz, Susan M. ; Leibovich, Bradley C. ; Blute, Michael L. ; Cheville, John C. ; Kwon, Eugene D. / B7-H4 expression in renal cell carcinoma and tumor vasculature : Associations with cancer progression and survival. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 27. pp. 10391-10396.
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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.",
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T2 - Associations with cancer progression and survival

AU - Krambeck, Amy E.

AU - Thompson, R. Houston

AU - Dong, Haidong M

AU - Lohse, Christine M.

AU - Park, Eugene S.

AU - Kuntz, Susan M.

AU - Leibovich, Bradley C.

AU - Blute, Michael L.

AU - Cheville, John C.

AU - Kwon, Eugene D

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AB - 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.

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KW - Kidney neoplasms

KW - Tumor biomarker

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