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

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

Research output: Contribution to journalArticle

54 Scopus 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.

Original languageEnglish (US)
Pages (from-to)2174-2180
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - Mar 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chavin, G., Sheinin, Y., Crispen, P. L., Boorjian, S. A., Roth, T. J., Rangel, L., Blute, M. L., Sebo, T. J., Tindall, D. J., Kwon, E. D., & Karnes, R. J. (2009). Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases. Clinical Cancer Research, 15(6), 2174-2180. https://doi.org/10.1158/1078-0432.CCR-08-2262