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

Clin Cancer Res. 2009 Mar 15;15(6):2174-80. doi: 10.1158/1078-0432.CCR-08-2262. Epub 2009 Mar 10.

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.

MeSH terms

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

Substances

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