title: Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.
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.
authors.affiliation: Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gillett
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: W Scott
authors.initials: WS
authors.lastname: Webster
authors.forename: Kent G
authors.initials: KG
authors.lastname: Krejci
authors.forename: John R
authors.initials: JR
authors.lastname: Lobo
authors.forename: Shomik
authors.initials: S
authors.lastname: Sengupta
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Horst
authors.initials: H
authors.lastname: Zincke
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
mesh_terms: D015703:Antigens, CD; D018122:B7-1 Antigen / Q000032:analysis*; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D007109:Immunity; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis; D016017:Odds Ratio; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides