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

Abstract

The online version of this article has a Supplementary Appendix. BackgroundGene 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 MethodsWe 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. ResultsWe 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-γ, 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. ConclusionsThe 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.Citation: Van Loo P, Tousseyn T, Vanhentenrijk V, Dierickx D, Malecka A, Vanden Bempt I, Verhoef G, Delabie J, Marynen P, Matthys P, and De Wolf-Peeters C. T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response. Haematologica. 2010;95:440-448. doi:10.3324/haematol.2009 This is an open-access paper. T-cell/histiocyte-rich large B-cell lymphoma shows transcriptional features suggestive of a tolerogenic host immune response

T cell/histiocyte-rich large B-cell lymphoma: an update on its biology and classification

“…In THRLBCL, large IDO expressing dendritic cells are located in the vicinity of tumor cells and this is not observed in NLPHL. Nearly all stromal components, but not the neoplastic cells, in THRLBCL express STAT1, while in NLPHL STAT1 expression is confined to large dendritic cells adjacent to the T-cell rosettes and some weak expression is discerned in the popcorn cells [23].…”

“…In contrast, in THRBCL typically affecting the extrafollicular compartment, these follicle mantles and FDC networks are lacking. Alternatively, to FDC stainings, IgD staining can be used to show the presence of residual IgD+ follicle mantles that favor NLPHL [23] above THRBCL. In THRLBCL, large IDO expressing dendritic cells are located in the vicinity of tumor cells and this is not observed in NLPHL.…”

“…To investigate whether the microenvironment surrounding the neoplastic cells of THRBCL could play an important role in determining the clinical outcome in THRLBCL, we investigated the functional meaning and the biological significance of this distinctive stroma by comparing the gene expression profile of whole tissue sections from THRLBCL cases (with prominent histiocytic component) with that of NLPHL [23]. Our GEP profiles of THRLBCL indicate a macrophage/histiocyte-activated status by which the tumor cells acquire several mechanisms to escape T cell-mediated immune surveillance by suppressing the proliferation and activation of effector T cells and their conversion to regulatory T cells.…”

Diffuse large B-cell lymphoma and Burkitt lymphoma

“…17 Immunohistochemical panel for investigation of DLBCL and BL Antibody Specificity Utility Cell proliferation Usually higher than 40% in DLBCL. Very high in BL (95e100%) Might correlate with prognosis, survival and recurrence in DLBCL GCET-1…”

Matched-Pair Analysis Comparing the Outcomes of T Cell/Histiocyte-Rich Large B Cell Lymphoma and Diffuse Large B Cell Lymphoma in Patients Treated with Rituximab-CHOP

“…Similar to follicular lymphoma and classical Hodgkin's lymphoma [20,21], it has been suggested that distinctive characteristics of the microenvironment surrounding malignant cells could affect clinical outcomes of THRLBCL. Indeed, the gene expression profile of THRLBCL shows features suggestive of a distinct tolerogenic host immune response that may play a key role in the aggressive behavior of THRLBCL [22]. The unique features of the THRLBCL microenvironment include the presence of CD68-positive histiocytes/macrophages.…”