BMSEHA15
Published online 1 October 2009
Haematologica, Vol 95, Issue 3, 440-448 doi:10.3324/haematol.2009.009647
Copyright © 2010 by Ferrata Storti Foundation
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Malignant Lymphomas

T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response

Peter Van Loo1,2,3, Thomas Tousseyn4, Vera Vanhentenrijk4, Daan Dierickx5, Agnieszka Malecka6, Isabelle Vanden Bempt4, Gregor Verhoef5, Jan Delabie6, Peter Marynen1,2, Patrick Matthys7, Chris De Wolf-Peeters4

1 Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium;
2 Department of Human Genetics, K.U. Leuven, Leuven, Belgium;
3 Bioinformatics Group, Department of Electrical Engineering, K.U. Leuven, Leuven, Belgium;
4 Department of Pathology, University Hospitals K.U. Leuven, Leuven, Belgium;
5 Department of Hematology, University Hospitals K.U. Leuven, Leuven, Belgium;
6 Department of Pathology, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway and
7 Department of Microbiology and Immunology, Rega Institute for Medical Research, K.U. Leuven, Leuven, Belgium

Correspondence: Patrick Matthys, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: Patrick.Matthys{at}rega.kuleuven.be, or Chris De Wolf-Peeters, Department of Pathology, University Hospitals K.U. Leuven, Minderbroedersstraat 12, B-3000 Leuven, E-mail: Christiane.Peeters{at}uz.kuleuven.be

Background: Gene expression profiling has successfully identified the prognostic significance of the host response in lymphomas. The aggressive T-cell/histiocyte-rich large B-cell lymphoma and the indolent nodular lymphocyte-predominant Hodgkin’s lymphoma are both characterized by a paucity of tumor cells embedded in an overwhelming background. The tumor cells of both lymphomas share several characteristics, while the cellular composition of their microenvironment is clearly different.

Design and Methods: We collected 33 cases of T-cell/histiocyte-rich large B-cell lymphoma and 56 cases of nodular lymphocyte-predominant Hodgkin’s lymphoma and performed microarray gene expression profiling on ten cases of each lymphoma, to obtain a better understanding of the lymphoma host response. By quantitative reverse transcriptase polymerase chain reaction we verified that these 20 selected cases were representative of the entire population of T-cell/histiocyte-rich large B-cell and nodular lymphocyte-predominant Hodgkin’s lymphomas.

Results: We observed that the microenvironment in nodular lymphocyte-predominant Hodgkin’s lymphoma is molecularly very similar to a lymph node characterized by follicular hyperplasia, while the microenvironment in T-cell/histiocyte-rich large B-cell lymphoma is clearly different. The T-cell/histiocyte-rich large B-cell lymphoma signature is hallmarked by up-regulation of CCL8, interferon-{gamma}, indoleamine 2,3 dioxygenase, VSIG4 and Toll-like receptors. These features may be responsible for the recruitment and activation of T cells, macrophages and dendritic cells, characterizing the stromal component of this lymphoma, and may point towards innate immunity and a tumor tolerogenic immune response in T-cell/histiocyte-rich large B-cell lymphoma.

Conclusions: The gene expression profile of T-cell/histiocyte-rich large B-cell lymphoma, in comparison with that of nodular lymphocyte-predominant Hodgkin’s lymphoma, shows features suggestive of a distinct tolerogenic host immune response that may play a key role in the aggressive behavior of this lymphoma, and that may serve as a potential target for future therapy.

Key words: gene expression profiling, Hodgkin’s lymphoma, THRLBCL.


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S. Pittaluga and E. S. Jaffe
T-cell/histiocyte-rich large B-cell lymphoma
Haematologica, March 1, 2010; 95(3): 352 - 356.
[Full Text] [PDF]