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Blood, 19 March 2009, Vol. 113, No. 12, pp. 2765-3775. Prepublished online as a Blood First Edition Paper on December 18, 2008; DOI 10.1182/blood-2008-07-168096.
Submitted July 11, 2008
Department of Bio-Pathology, Molecular Oncology, Hematology, and Tumor Immunology, Institut Paoli-Calmettes and Universite de la Mediterranee, Marseille, France * Corresponding author; email: xerril{at}marseille.fnclcc.fr.
The outcome of classical Hodgkin's lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by EBV infection. To characterize the cHL microenvironment, a set of 63 cHL tissue samples was profiled using DNA microarrays. Their gene expression profile differed from that of T-cell rich B-cell lymphoma (TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in TCRBCL. EBV+ cHL tissues could be distinguished from EBV- samples by a gene signature characteristic of Th1 and antiviral responses. Samples from cHL patients with favorable outcome overexpressed genes specific of B-cells and genes involved in apoptotic pathways. An independent set of 146 cHL samples was analyzed using immunohistochemistry. It showed a significant adverse value in case of high percentage of either TIA-1+ reactive cells or topoisomerase-2+ tumor cells, whereas high numbers of BCL11A+, FOXP3+ or CD20+ reactive cells had a favorable influence. Immunodetection of BCL11A, a marker of both B-cells and plasmacytoid dendritic cells, had the strongest predictive value. Our results suggest an antitumoral role for B-cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in TCRBCL than cHL. The observation of Th1/ anti-viral response in EBV+ cHL tissues provides a basis for novel treatment strategies.
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