Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases.

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.

• Authors: Grant Chavin, Yuri Sheinin, Paul L Crispen, Stephen A Boorjian, Timothy J Roth, Laureano Rangel, Michael L Blute, Thomas J Sebo, Don J Tindall, Eugene D Kwon, R Jeffrey Karnes
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 6 Pg. 2174-80 (Mar 15 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19276267 (Publication Type: Journal Article)

Chemical References

• Androgen Antagonists
• Antigens, CD
• B7 Antigens
• CD276 protein, human
• Receptors, Immunologic

Topics

• Adult
• Aged
• Androgen Antagonists (therapeutic use)
• Antigens, CD (analysis)
• B7 Antigens
• Bone Neoplasms (secondary)
• Humans
• Male
• Middle Aged
• Prostatic Neoplasms (drug therapy, immunology, pathology)
• Receptors, Immunologic (analysis)
• T-Lymphocytes (immunology)