Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases.
OBJECTIVE
Prostate cancer cells uniformly express the immune cell inhibitory B7-H3 ligand. Enhanced B7-H3 expression correlates with increased disease progression and cancer-specific death after radical prostatectomy (RP).


METHODS
To further assess whether B7-H3 expression is hormone regulated and persists as a viable target during (or after) androgen-ablative therapy, we examined B7-H3 ligand expression within primary and metastatic cancer lesions in response to neoadjuvant hormone therapy (NHT) or palliative hormone deprivation. Tumor B7-H3 in RP specimens from men treated with >/=3 months of NHT was compared with B7-H3 in tumors from matched patients who received no therapy before RP. Hormone-treated and untreated metastatic lesions involving bone were also compared for levels of B7-H3 expression.


RESULTS
Of 165 consecutive RP specimens in each cohort studied, sufficient tissues were available for 148 patients (89.7%) treated with NHT versus 127 patients (77.0%) treated with surgery alone. B7-H3 was expressed in 142 (95.9%) tumors from NHT patients compared with 122 (96.0%) tumors from patients treated with surgery alone (P = 0.91). B7-H3 expression intensity in RP specimens was not affected by NHT (P = 0.12). Bone metastases from 11 (32.4%) untreated and 23 (67.6%) androgen-ablated patients revealed that B7-H3 expression increased in response to hormone therapy (P = 0.04) relative to untreated lesions.


CONCLUSIONS
Taken together, B7-H3 expression seems to remain stable (or may even increase) in response to hormone therapy. As such, B7-H3 may represent an attractive target to improve treatment of men with high-risk hormone-treated or refractory prostate cancer.
Chavin
Grant
G
Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
Sheinin
Yuri
Y
Crispen
Paul L
PL
Boorjian
Stephen A
SA
Roth
Timothy J
TJ
Rangel
Laureano
L
Blute
Michael L
ML
Sebo
Thomas J
TJ
Tindall
Don J
DJ
Kwon
Eugene D
ED
Karnes
R Jeffrey
RJ
D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis*; D060887:B7 Antigens; D001859:Bone Neoplasms / Q000556:secondary*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology
D000726:Androgen Antagonists; D015703:Antigens, CD; D060887:B7 Antigens; C423237:CD276 protein, human; D011971:Receptors, Immunologic