B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome.
B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P = 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P = 0.005) and cancer-specific death (P = 0.004 and P = 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.
Zang
Xingxing
X
Howard Hughes Medical Institute, Immunology Program and Ludwig Center for Cancer Immunotherapy, and Departments of Surgery and Urology, Pathology, and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Thompson
R Houston
RH
Al-Ahmadie
Hikmat A
HA
Serio
Angel M
AM
Reuter
Victor E
VE
Eastham
James A
JA
Scardino
Peter T
PT
Sharma
Padmanee
P
Allison
James P
JP
D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000032:analysis / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism*; D016019:Survival Analysis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D015703:Antigens, CD; D060887:B7 Antigens; D018122:B7-1 Antigen; C423237:CD276 protein, human; D011971:Receptors, Immunologic; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human