Costimulatory B7-H1 in renal cell carcinoma patients

Indicator of tumor aggressiveness and potential therapeutic target

R. Houston Thompson, Michael D. Gillett, John C. Cheville, Christine M. Lohse, Haidong M 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

Research output: Contribution to journalArticle

545 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17174-17179
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number49
DOIs
StatePublished - Dec 7 2004

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Renal Cell Carcinoma
Neoplasms
Therapeutics
Lymphocytes
Immunity
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Immunotherapy
Cell Survival
Glycoproteins
Macrophages
Odds Ratio
Confidence Intervals
Kidney

Keywords

  • Costimulation
  • Immunotherapy
  • T lymphocyte
  • Tumor biomarker

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Costimulatory B7-H1 in renal cell carcinoma patients : Indicator of tumor aggressiveness and potential therapeutic target. / Thompson, R. Houston; Gillett, Michael D.; Cheville, John C.; Lohse, Christine M.; Dong, Haidong M; 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 49, 07.12.2004, p. 17174-17179.

Research output: Contribution to journalArticle

Thompson, RH, Gillett, MD, Cheville, JC, Lohse, CM, Dong, HM, Webster, WS, Krejci, KG, Lobo, JR, Sengupta, S, Chen, L, Zincke, H, Blute, ML, Strome, SE, Leibovich, BC & Kwon, ED 2004, 'Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 49, pp. 17174-17179. https://doi.org/10.1073/pnas.0406351101
Thompson, R. Houston ; Gillett, Michael D. ; Cheville, John C. ; Lohse, Christine M. ; Dong, Haidong M ; 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. / Costimulatory B7-H1 in renal cell carcinoma patients : Indicator of tumor aggressiveness and potential therapeutic target. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 49. pp. 17174-17179.
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T2 - Indicator of tumor aggressiveness and potential therapeutic target

AU - Thompson, R. Houston

AU - Gillett, Michael D.

AU - Cheville, John C.

AU - Lohse, Christine M.

AU - Dong, Haidong M

AU - Webster, W. Scott

AU - Krejci, Kent G.

AU - Lobo, John R.

AU - Sengupta, Shomik

AU - Chen, Lieping

AU - Zincke, Horst

AU - Blute, Michael L.

AU - Strome, Scott E.

AU - Leibovich, Bradley C.

AU - Kwon, Eugene D

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N2 - 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.

AB - 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.

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