title: Macrophages in T cell/histiocyte rich large B cell lymphoma strongly express metal-binding proteins and show a bi-activated phenotype.
abstract: Abundant macrophage infiltration in tumors often correlates with a poor prognosis. T cell/histiocyte rich large B cell lymphoma (THRLBCL) is a distinct aggressive B cell lymphoma entity showing a high macrophage content. To further elucidate the role of tumor-associated macrophages in THRLBCL, we performed gene expression profiling of microdissected histiocyte subsets of THRLBCL, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), Piringer lymphadenitis, sarcoidosis, nonspecific lymphadenitis and monocytes from peripheral blood. In a supervised principal component analysis, histiocytes from THRLBCL were most closely related to epithelioid cells from NLPHL, with both types of cells expressing genes related to proinflammatory and regulatory macrophage activity. Moreover, histiocytes from THRLBCL strongly expressed metal-binding proteins like MT2A, by which histiocytes of THRLBCL can be distinguished from the other histiocyte subsets investigated. Interestingly, the validation at the protein level showed a strong expression of TXN, CXCL9, MT2A and SOD2 not only in macrophages of THRLBCL but also in the tumor cells of NLPHL and classical Hodgkin lymphoma (cHL). Overall, the present findings indicate that macrophages in the microenvironment of THRLBCL have acquired a distinct gene expression pattern that is characterized by a mixed M1/M2 phenotype and a strong expression of several metal binding proteins. The microenvironments in NLPHL and THRLBCL appear to have a similar influence on the macrophage phenotype. The high expression of metal binding proteins in histiocytes of THRLBCL may be diagnostically useful, but a potential pathophysiological role remains to be identified.
authors.affiliation: Senckenberg Institute of Pathology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Tousseyn
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.forename: Patricia
authors.initials: P
authors.lastname: Flüchter
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.forename: An
authors.initials: A
authors.lastname: Herreman
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Chris
authors.initials: C
authors.lastname: de Wolf-Peeters
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Christian
authors.initials: C
authors.lastname: Steidl
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
mesh_terms: D054370:Chemokine CXCL9 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis; D009367:Neoplasm Staging; D011379:Prognosis; D013482:Superoxide Dismutase / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013879:Thioredoxins / Q000096:biosynthesis; D000099156:Superoxide Dismutase 2
chemical_list: D054370:Chemokine CXCL9; D008668:Metallothionein; D013482:Superoxide Dismutase; D013879:Thioredoxins; D000099156:Superoxide Dismutase 2; C080810:CXCL9 protein, human; C491053:MT2A protein, human; C491203:TXN protein, human
keywords: T cell/histiocyte rich B cell lymphoma; gene expression profiling; macrophages; nodular lymphocyte predominant Hodgkin lymphoma