Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome

The outcome of classical Hodgkin lymphoma (cHL) patients may be related to the tumor microenvironment, which in turn may be influenced by Epstein-Barr virus (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 histiocyte T cell rich B-cell lymphoma (H/TCRBCL) samples that were used as controls, mainly due to high expression of PDCD1/PD-1 in H/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 for 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. Our results suggest an antitumoral role for B cells in the cHL microenvironment and a stronger stromal influence of the PD1 pathway in H/TCRBCL than cHL. The observation of Th1/antiviral response in EBV+ cHL tissues provides a basis for novel treatment strategies. (Blood. 2009;113:2765-2775)