Kube, Dieter

[["dc.bibliographiccitation.firstpage","399"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","409"],["dc.bibliographiccitation.volume","230"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Wei, Wenbin"],["dc.contributor.author","Nagy, Eszter"],["dc.contributor.author","Prouzova, Zuzana"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Rowe, Martin"],["dc.contributor.author","Woodman, Ciaran B."],["dc.contributor.author","Murray, Paul G."],["dc.date.accessioned","2018-11-07T09:21:37Z"],["dc.date.available","2018-11-07T09:21:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Hodgkin's lymphoma is unusual among B cell lymphomas, in so far as the malignant Hodgkin/Reed-Sternberg (HRS) cells lack a functional B cell receptor (BCR), as well as many of the required downstream signalling components. In Epstein-Barr virus (EBV)-positive cases of Hodgkin's lymphoma, HRS cells express the viral latent membrane proteins (LMP)-1 and -2A. LMP2A is thought to contribute to the pathogenesis of Hodgkin's lymphoma by providing a surrogate BCR-like survival signal. However, LMP2A has also been shown to induce the virus-replicative cycle in B cells, an event presumably incompatible with lymphomagenesis. In an attempt to resolve this apparent paradox, we compared the transcriptional changes observed in primary HRS cells with those induced by LMP2A and by BCR activation in primary human germinal centre (GC) B cells, the presumed progenitors of HRS cells. We found a subset of genes that were up-regulated by both LMP2A expression and BCR activation but which were down-regulated in primary HRS cells. These genes included EGR1, an immediate-early gene that is required for BCR-induced entry to the virus-replicative cycle. We present data supporting a model for the pathogenesis of EBV-positive Hodgkin's lymphoma in which LMP2A-expressing HRS cells lacking BCR signalling functions cannot induce EGR1 and are consequently protected from entry to the virus lytic cycle. The primary microarray data are available from GEO (http://www.ncbi.nlm.nih.gov/geo/) under series Accession No 46143. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd."],["dc.identifier.doi","10.1002/path.4198"],["dc.identifier.isi","000326160000007"],["dc.identifier.pmid","23592216"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29152"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1096-9896"],["dc.relation.issn","0022-3417"],["dc.title","Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","598"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","605"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Pinkert, D."],["dc.contributor.author","Smola-Hess, S."],["dc.contributor.author","Michels, A."],["dc.contributor.author","Ransohoff, Richard M."],["dc.contributor.author","Tesch, H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T11:07:44Z"],["dc.date.available","2018-11-07T11:07:44Z"],["dc.date.issued","2005"],["dc.description.abstract","The latent membrane protein 1 (LMP1) of Epstein-Barr Virus (EBV) is the main inducer of immuno-modulatory molecules affecting growth and survival of EBV-infected cells. However, the network of signalling pathways involved remains to be elucidated. Here we show that LMP1 may regulate cellular genes like IFN-gamma-inducible protein-10 kDa (IP-10) not only through transcriptional but also post-transcriptional mechanisms. LMP1-mediated IP-10 expression is independent from IFN-gamma, TNF-alpha or IL-18. Transcriptional activation of IP-10 by LMP1 or CD40 stimulation depends on an NF-KB motif within the proximal 435 bp fragment. Carboxy-terminal activating regions 1 or 2 of LMP1 are sufficient to direct IP-10 promoter activation. IP-10 induction is inhibited by blockade of p38/SAPK2 with SB 202190, which results in decreased IP-10 mRNA half-life without affecting IP-10 promoter activity. Thus, LMP1-mediated p38/SAPK2 activation regulates transcript stability. This new mechanism of gene regulation demonstrates the potential of the oncoprotein LMP1 to orchestrate a network of signalling pathways at different regulatory levels including mRNA stability. (C) 2004 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/ijc.20759"],["dc.identifier.isi","000227535400012"],["dc.identifier.pmid","15578697"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52637"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0020-7136"],["dc.title","The Epstein-Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP-10: Importance of mRNA half-life regulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","43"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","Ulrich, Antje"],["dc.contributor.author","Matulewicz, Kamila"],["dc.contributor.author","Lenze, Dido"],["dc.contributor.author","Hummel, Michael"],["dc.contributor.author","Kieser, Arnd"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T09:02:13Z"],["dc.date.available","2018-11-07T09:02:13Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Aggressive Non-Hodgkin lymphomas (NHL) are a group of lymphomas derived from germinal centre B cells which display a heterogeneous pattern of oncogenic pathway activation. We postulate that specific immune response associated signalling, affecting gene transcription networks, may be associated with the activation of different oncogenic pathways in aggressive Non-Hodgkin lymphomas (NHL). Methodology: The B cell receptor (BCR), CD40, B-cell activating factor (BAFF)-receptors and Interleukin (IL) 21 receptor and Toll like receptor 4 (TLR4) were stimulated in human transformed germinal centre B cells by treatment with anti IgM F(ab)(2)-fragments, CD40L, BAFF, IL21 and LPS respectively. The changes in gene expression following the activation of Jak/STAT, NF-kappa B, MAPK, Ca2+ and PI3K signalling triggered by these stimuli was assessed using microarray analysis. The expression of top 100 genes which had a change in gene expression following stimulation was investigated in gene expression profiles of patients with Aggressive non-Hodgkin Lymphoma (NHL). Results: alpha IgM stimulation led to the largest number of changes in gene expression, affecting overall 6596 genes. While CD40L stimulation changed the expression of 1194 genes and IL21 stimulation affected 902 genes, only 283 and 129 genes were modulated by lipopolysaccharide or BAFF receptor stimulation, respectively. Interestingly, genes associated with a Burkitt-like phenotype, such as MYC, BCL6 or LEF1, were affected by alpha IgM. Unique and shared gene expression was delineated. NHL-patients were sorted according to their similarity in the expression of TOP100 affected genes to stimulated transformed germinal centre B cells The alpha IgM gene module discriminated individual DLBCL in a similar manner to CD40L or IL21 gene modules. DLBCLs with low module activation often carry chromosomal MYC aberrations. DLBCLs with high module activation show strong expression of genes involved in cell-cell communication, immune responses or negative feedback loops. Using chemical inhibitors for selected kinases we show that mitogen activated protein kinase-and phosphoinositide 3 kinase-signalling are dominantly involved in regulating genes included in the alpha IgM gene module. Conclusion: We provide an in vitro model system to investigate pathway activation in lymphomas. We defined the extent to which different immune response associated pathways are responsible for differences in gene expression which distinguish individual DLBCL cases. Our results support the view that tonic or constitutively active MAPK/ERK pathways are an important part of oncogenic signalling in NHL. The experimental model can now be applied to study the therapeutic potential of deregulated oncogenic pathways and to develop individual treatment strategies for lymphoma patients."],["dc.identifier.doi","10.1186/1478-811X-10-43"],["dc.identifier.isi","000314937400001"],["dc.identifier.pmid","23253402"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8528"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24629"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1478-811X"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","HAEMATOLOGICA-THE HEMATOLOGY JOURNAL"],["dc.bibliographiccitation.volume","92"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Morgan, S. L."],["dc.contributor.author","Kuo, M."],["dc.contributor.author","Wei, W."],["dc.contributor.author","Chukwuma, M. B."],["dc.contributor.author","Arrand, John R."],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Gordon, Jennifer"],["dc.contributor.author","Young, L. S."],["dc.contributor.author","Woodman, Ciaran B."],["dc.contributor.author","Murray, Paul G."],["dc.date.accessioned","2018-11-07T10:56:48Z"],["dc.date.available","2018-11-07T10:56:48Z"],["dc.date.issued","2007"],["dc.format.extent","41"],["dc.identifier.isi","000250470800107"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50102"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ferrata Storti Foundation"],["dc.publisher.place","Pavia"],["dc.relation.conference","7th International Symposium on Hodgkin Lymphoma"],["dc.relation.eventlocation","Cologne, GERMANY"],["dc.relation.issn","0390-6078"],["dc.title","The EBV-encoded latent membrane protein-1 imposes on normal human germinal center B cells, a Hodgkin/Reed-Sternberg-like gene expression signature"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","593"],["dc.bibliographiccitation.issue","5709"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","596"],["dc.bibliographiccitation.volume","307"],["dc.contributor.author","Paludan, C."],["dc.contributor.author","Schmid, D."],["dc.contributor.author","Landthaler, M."],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Tuschl, T."],["dc.contributor.author","Münz, Christian"],["dc.date.accessioned","2018-11-07T08:31:51Z"],["dc.date.available","2018-11-07T08:31:51Z"],["dc.date.issued","2005"],["dc.description.abstract","CD4(+) T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4(+) T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4(+) T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease."],["dc.identifier.doi","10.1126/science.1104904"],["dc.identifier.isi","000226694000051"],["dc.identifier.pmid","15591165"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17213"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0036-8075"],["dc.title","Endogenous MHC class II processing of a viral nuclear antigen after autophagy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EJC SUPPLEMENTS"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Bentink, Stefan"],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Lenze, Dido"],["dc.contributor.author","Hummel, Michael"],["dc.contributor.author","Kuo, M."],["dc.contributor.author","Murray, P."],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Vockerodt, Martina"],["dc.date.accessioned","2018-11-07T08:42:32Z"],["dc.date.available","2018-11-07T08:42:32Z"],["dc.date.issued","2010"],["dc.format.extent","107"],["dc.identifier.isi","000288603100400"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19723"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.publisher.place","Oxford"],["dc.relation.conference","21st Meeting of the European-Association-for-Cancer-Research"],["dc.relation.eventlocation","Oslo, NORWAY"],["dc.relation.issn","1359-6349"],["dc.title","A c-Myc induced gene expression signature in human germinal center B cells predicts subtypes of aggressive non-Hodgkin Lymphoma"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","459"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Genes and Immunity"],["dc.bibliographiccitation.lastpage","468"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Mormann, M."],["dc.contributor.author","Tomiuk, J."],["dc.contributor.author","Rieth, H."],["dc.contributor.author","Hua, Thanh-Duc"],["dc.contributor.author","Kremsner, P. G."],["dc.contributor.author","Vockerodt, Martina"],["dc.date.accessioned","2018-11-07T10:35:46Z"],["dc.date.available","2018-11-07T10:35:46Z"],["dc.date.issued","2003"],["dc.description.abstract","Different cytokine genotypes exist in the population, for example, as a result of selective pressure of infectious diseases. It may be that specific cytokine genotypes that are beneficial by creating a 'proinflammatory' phenotype predispose to severe inflammatory disease with worse clinical outcome. There is individual variation in the production of certain cytokines in relation to their genotypes. IL-10, IFN-gamma and TNF-alpha are key components in the regulation of immune responses and the balance of their expression levels is predictive in certain diseases. To describe cytokine genotypes, a one-tube PCR reaction was developed to analyse simultaneously DNA sequence variations of cytokine genes IL-10, IFN-gamma, and TNF. This multiplex PCR approach was used to provide genotypic data for two geographically independent donor groups from Germany and Gabon. Significant differences were obtained for the majority of sequence variations comparing both populations. However, the SNPs within the 5'-flanking region of the IL-10 gene at position -1087 and -6208 are comparable in their genic and genotypic behaviour. Comparing allelic and genotypic disequilibrium between pairs of loci revealed different association patterns for both populations according to the geographical polymorphism. This assay may improve immunogenetic studies in disease, characterized by disbalanced IL-10, IFN-gamma and TNF-alpha expression."],["dc.identifier.doi","10.1038/sj.gene.6364003"],["dc.identifier.isi","000185970500001"],["dc.identifier.pmid","14551598"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45168"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1466-4879"],["dc.title","Simultaneous analysis of interleukin-10 gene microsatellites and single-nucleotide polymorphisms in parallel with tumour necrosis factor and interferon-gamma short tandem repeats by fluorescence-based polymerase chain reaction"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","142"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","154"],["dc.bibliographiccitation.volume","248"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Vrzalikova, Katerina"],["dc.contributor.author","Ibrahim, Maha"],["dc.contributor.author","Nagy, Eszter"],["dc.contributor.author","Margielewska, Sandra"],["dc.contributor.author","Hollows, Robert"],["dc.contributor.author","Lupino, Lauren"],["dc.contributor.author","Tooze, Reuben"],["dc.contributor.author","Care, Matthew"],["dc.contributor.author","Simmons, William"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Perry, Tracey"],["dc.contributor.author","Abdullah, Maizaton"],["dc.contributor.author","Foster, Stephen"],["dc.contributor.author","Reynolds, Gary"],["dc.contributor.author","Dowell, Alexander"],["dc.contributor.author","Rudzki, Zbigniew"],["dc.contributor.author","Krappmann, Daniel"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Woodman, Ciaran"],["dc.contributor.author","Wei, Wenbin"],["dc.contributor.author","Taylor, Graham"],["dc.contributor.author","Murray, Paul G"],["dc.date.accessioned","2020-12-10T14:07:02Z"],["dc.date.available","2020-12-10T14:07:02Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1002/path.5237"],["dc.identifier.eissn","1096-9896"],["dc.identifier.issn","0022-3417"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70111"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC‐subtype diffuse large B‐cell lymphoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","640"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","British Journal of Haematology"],["dc.bibliographiccitation.lastpage","646"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Belge, G."],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Irsch, J."],["dc.contributor.author","Siebert, Reiner"],["dc.contributor.author","Tesch, H."],["dc.contributor.author","Diehl, Volker"],["dc.contributor.author","Wolf, J."],["dc.contributor.author","Bullerdiek, J."],["dc.contributor.author","Staratschek-Jox, A."],["dc.date.accessioned","2018-11-07T09:43:49Z"],["dc.date.available","2018-11-07T09:43:49Z"],["dc.date.issued","2002"],["dc.description.abstract","In the vast majority of cases, Hodgkin - Reed Sternberg (H-RS) cells, the malignant cells in Hodgkin's lymphoma (HL), are derived from germinal centre B cells. In some cases, somatic mutations within the rearranged immunoglobulin heavy (IgH) chain genes were detected, rendering potentially functional gene rearrangements nonfunctional. In these H-RS cells the expression of high-affinity B-cell receptors (BCR) was prevented. As in other cases only one non-productive IgH chain gene rearrangement was amplified from H-RS cells, it was speculated whether, in these cases, the functionally rearranged IgH chain genes were lost. An alternative explanation might be that the rearranged genes could not be amplified owing to a high load of somatic mutations within the primer binding sites. Here, we showed that, in the HL-derived Epstein - Barr virus (EBV)-positive cell line L591, only one non-functional somatically mutated IgH gene rearrangement could be detected. The other potentially functional IgH gene rearrangement was lost as a result of an unbalanced translocation affecting the long arm of chromosome 14. Moreover, L591 cells express the EBV latent membrane proteins LMP1 and LMP2A, which might have contributed to the 'escape' of these cells from apoptosis within the germinal centre. We conclude that, apart from the introduction of 'crippling mutations' into the rearranged VDJ genes rearrangement, deletions of the IGH locus may be regarded as another mechanism to prevent the expression of a BCR in H-RS cells."],["dc.identifier.doi","10.1046/j.1365-2141.2002.03894.x"],["dc.identifier.isi","000179283600010"],["dc.identifier.pmid","12437638"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34263"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Ltd"],["dc.relation.issn","0007-1048"],["dc.title","An unbalanced translocation involving chromosome 14 is the probable cause for loss of potentially functional rearranged immunoglobulin heavy chain genes in the Epstein-Barr virus-positive Hodgkin's lymphoma-derived cell line L591"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","571"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Oncology"],["dc.bibliographiccitation.lastpage","589"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Arlt, Annekatrin"],["dc.contributor.author","Bonin, Frederike"],["dc.contributor.author","Rehberg, Thorsten"],["dc.contributor.author","Perez‐Rubio, Paula"],["dc.contributor.author","Engelmann, Julia C."],["dc.contributor.author","Limm, Katharina"],["dc.contributor.author","Reinke, Sarah"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Sun, Xueni"],["dc.contributor.author","Specht, Rieke"],["dc.contributor.author","Maulhardt, Markus"],["dc.contributor.author","Linke, Franziska"],["dc.contributor.author","Bunt, Gertrude"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Wilting, Jörg"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dettmer, Katja"],["dc.contributor.author","Gronwald, Wolfram"],["dc.contributor.author","Oefner, Peter J."],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2021-04-14T08:27:44Z"],["dc.date.available","2021-04-14T08:27:44Z"],["dc.date.issued","2020"],["dc.description.abstract","Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination."],["dc.description.abstract","The study highlights the ability of Hodgkin lymphoma cells to attract and to differentiate monocytes into M2‐like Mφ and the role of IL13 in regulating CD206 but also that CD206 contributes to the remodeling of the tumor microenvironment via take up glycoconjugates as well as type‐I collagen and immunosuppression by PD‐L1 upregulation. image"],["dc.description.sponsorship","Stiftung der Georg‐August‐Universität"],["dc.description.sponsorship","Wilhelm‐Sander‐Stiftung"],["dc.description.sponsorship","Deutsche Krebshilfe http://dx.doi.org/10.13039/501100005972"],["dc.description.sponsorship","Bundesministerium für Bildung und Forschung http://dx.doi.org/10.13039/501100002347"],["dc.description.sponsorship","Interreg"],["dc.identifier.doi","10.1002/1878-0261.12616"],["dc.identifier.eissn","1878-0261"],["dc.identifier.issn","1574-7891"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82387"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1878-0261"],["dc.relation.issn","1574-7891"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]