Expression of Immunosuppresive B7-H3 Ligand by Hormone-Treated Prostate Cancer Tumors and Metastases

Department of Urology, Mayo Clinic, Rochester, Minnesota, USA.
Clinical Cancer Research (Impact Factor: 8.72). 03/2009; 15(6):2174-80. DOI: 10.1158/1078-0432.CCR-08-2262
Source: PubMed


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).
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.
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.
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.

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    • "Like many other B7 family members, B7-H3 is expressed not only in immune cells, including T cells, natural killer cells and antigen-presenting cells, but also in osteoblasts, fibroblasts , fibroblast-like synoviocytes, and epithelial cells, thus implying more diverse roles [18] [19]. Furthermore, B7-H3 has garnered an extraordinary amount of interest in autoimmune diseases [20] and has been linked to tumors, such as lung and prostate tumors [21] [22] [23]. While Suh et al. reported that the binding of B7-H3 to its unknown counter-receptor promoted osteoblastic differentiation and formation [19], little research has investigated its role in osteoporosis. "
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