Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.
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.
Thompson
R Houston
RH
Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
Gillett
Michael D
MD
Cheville
John C
JC
Lohse
Christine M
CM
Dong
Haidong
H
Webster
W Scott
WS
Krejci
Kent G
KG
Lobo
John R
JR
Sengupta
Shomik
S
Chen
Lieping
L
Zincke
Horst
H
Blute
Michael L
ML
Strome
Scott E
SE
Leibovich
Bradley C
BC
Kwon
Eugene D
ED
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
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010455:Peptides