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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    • "Recently discovered members of the B7-CD28 family, B7-H3, and B7x, were evaluated by IHC on pathological specimens from clinically localized PCa patients treated by RP [131, 132]. These studies concluded that B7-H3 was uniformly and aberrantly expressed in PCa and correlated to the worst clinical outcomes of this disease [131]. "
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    • "However, the reported functions of these two isoforms have been inconsistent, with some researches showing the costimulatory functions of B7-H3 in T cell responses [8], [9], [32], [38]–[40], and others revealing an inhibitory role in T cell responses [10]–[12], [33]. This inhibitory function of B7-H3 on T cell responses has led to further investigation into the association between B7-H3 expression and carcinoma progression [18], [25], [41], [42]. Results from these studies have indicated that the patients with strong B7-H3 expression on tumors were more likely to show disease spread. "
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    • "Moreover, B7-H3 has also been implicated as a potential coinhibitor of antitumor immunity. For example, several independent studies have shown that markedly increased expression of B7-H3 protein in human malignant tumor cells is associated with increased disease severity in breast cancer [19], colorectal carcinoma [30], hepatocellular carcinoma [31], prostate cancer [32], non-small-cell lung cancer [33] and neuroblastoma [34]. "
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