B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival.
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.
Krambeck
Amy E
AE
Departments of *Urology.
Thompson
R Houston
RH
Departments of *Urology.
Dong
Haidong
H
Immunology.
Lohse
Christine M
CM
Health Sciences Research, and.
Park
Eugene S
ES
Departments of *Urology.
Kuntz
Susan M
SM
Immunology.
Leibovich
Bradley C
BC
Departments of *Urology.
Blute
Michael L
ML
Departments of *Urology.
Cheville
John C
JC
Laboratory Medicine and Pathology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905.
Kwon
Eugene D
ED
Departments of *Urology, kwon.eugene@mayo.edu.|Immunology.
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human