Prostate cancer lesions are surrounded by FOXP3 + , PD-1 + and B7-H1 + lymphocyte clusters Kathleen Ebelt a,b,c, * , Gregor Babaryka d , Bernhard Frankenberger a , Christian G. Stief e , Wolfgang Eisenmenger f , Thomas Kirchner d , Dolores J. Schendel a,b , Elfriede Noessner a a Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Marchioninistr. 25, 81377 Munich, Germany b Clinical Cooperation Group ‘Immune Monitoring’, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Munich, Germany c Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universita ¨t Mu ¨ nchen, Munich, Germany d Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany e Department of Urology, University-Hospital Grosshadern, Hospital of the Ludwig-Maximilians-University, Munich, Germany f Institute of Legal Medicine, Ludwig-Maximilians-University, Munich, Germany ARTICLE INFO Article history: Received 30 November 2008 Received in revised form 1 February 2009 Accepted 11 February 2009 Available online 21 March 2009 Keywords: Tumour-infiltrating lymphocytes FOXP3 Tregs PD-1 B7-H1 Exhausted lymphocytes ABSTRACT The immune response against prostate cancer seems to be inefficient although tumour cells show an over-expression of tumour-associated antigens suggesting that regulatory networks inhibit immune cell function locally. To address this proposition, lymphocytes within prostate cancer-inflicted tissue were analysed for the expression of markers associ- ated with negative regulatory function and exhaustion. Prostate cancer, benign prostatic hyperplasia and healthy prostate tissues were investi- gated by immunohistology for CD25, FOXP3, PD-1 and B7-H1. We had previously documented that prostate cancer islets are surrounded by clustered accumulations of CD3 + lymphocytes, which lack perforin and interferon-gamma (IFNc) expression, thus are apparently quiescent. Here, we report that these clusters contain numerous CD25 + and FOXP3 + cells. These markers are associated with regulatory T cells, and their presence in lymphocyte clusters near prostate cancer regions indicates an envi- ronment with negative impact on immune response against cancer cells. Consistent with this hypothesis, cells expressing PD-1 and its ligand B7-H1, which are markers associated with exhaustion of lymphocyte function, were also detected in the lymphocyte clusters. Expression of molecules associated with inhibition and exhaustion of lymphocytes may reflect events contributing to ineffective immune responses against cancer cells. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Prostate cancer is the most common solid-organ cancer of men in Western countries and follows lung cancer as the sec- ond most frequent cancer-related cause of death. Among all malignant urological tumours, prostate cancer is the leading cause of death. 1,2 Despite its high incidence, the prognosis for patients with prostate cancer is excellent when the carci- 0959-8049/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejca.2009.02.015 * Corresponding author: Institute of Molecular Immunology, Helmholtz Center Munich, German Research Center for Environmental Health (GmbH), Marchioninistr. 25, 81377 Munich, Germany. Tel.: +49 89 4140 6623; fax: +49 89 4140 4880. E-mail address: ebelt.k@web.de (K. Ebelt). EUROPEAN JOURNAL OF CANCER 45 (2009) 1664 – 1672 available at www.sciencedirect.com journal homepage: www.ejconline.com