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Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases. Clin Cancer Res 2009 Mar 15;15(6):2174-80

Date

03/12/2009

Pubmed ID

19276267

Pubmed Central ID

PMC2676580

DOI

10.1158/1078-0432.CCR-08-2262

Scopus ID

2-s2.0-63549150834 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

PURPOSE: 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).

EXPERIMENTAL DESIGN: 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.

Author List

Chavin G, Sheinin Y, Crispen PL, Boorjian SA, Roth TJ, Rangel L, Blute ML, Sebo TJ, Tindall DJ, Kwon ED, Karnes RJ

Author

Yuri M. Sheinin MD, PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Androgen Antagonists
Antigens, CD
B7 Antigens
Bone Neoplasms
Humans
Male
Middle Aged
Prostatic Neoplasms
Receptors, Immunologic
T-Lymphocytes