Ruben A. L. de Groen, Fleur A. de Groot, Stefan Böhringer, Esther J. Kret, Lorraine M. de Haan, Troy Noordenbos, Susan Blommers, Romée E. W. Jansen, Tom van Wezel, Ronald van Eijk, Richard Raghoo, Dina Ruano, Liane te Boome, Valeska Terpstra, Henriette Levenga, Els Ahsmann, Eduardus F. M. Posthuma, Isabelle Focke-Snieders, Lizan Hardi, Wietske C. E. den Hartog, Anke van den Berg, Pim Mutsaers, King Lam, Marjolein W. M. van der Poel, Myrurgia Abdul Hamid, F. J. Sherida H. Woei-A-Jin, Ann Janssens, Thomas Tousseyn, Judith V. M. G. Bovée, Lianne Koens, Arjan Diepstra, Arjen H. G. Cleven, Marie José Kersten, Patty M. Jansen, Hendrik Veelken, Marcel Nijland, Tim J. A. Dekker, Joost S. P. Vermaat
{"title":"具有丰富免疫肿瘤微环境的骨弥漫性大B细胞淋巴瘤生存率高","authors":"Ruben A. L. de Groen, Fleur A. de Groot, Stefan Böhringer, Esther J. Kret, Lorraine M. de Haan, Troy Noordenbos, Susan Blommers, Romée E. W. Jansen, Tom van Wezel, Ronald van Eijk, Richard Raghoo, Dina Ruano, Liane te Boome, Valeska Terpstra, Henriette Levenga, Els Ahsmann, Eduardus F. M. Posthuma, Isabelle Focke-Snieders, Lizan Hardi, Wietske C. E. den Hartog, Anke van den Berg, Pim Mutsaers, King Lam, Marjolein W. M. van der Poel, Myrurgia Abdul Hamid, F. J. Sherida H. Woei-A-Jin, Ann Janssens, Thomas Tousseyn, Judith V. M. G. Bovée, Lianne Koens, Arjan Diepstra, Arjen H. G. Cleven, Marie José Kersten, Patty M. Jansen, Hendrik Veelken, Marcel Nijland, Tim J. A. Dekker, Joost S. P. Vermaat","doi":"10.1038/s41408-025-01291-z","DOIUrl":null,"url":null,"abstract":"<p>With tumor genomic and gene-expression profiling (GEP), this study investigated the immune-molecular signatures of a unique cohort of diffuse large B-cell lymphoma of the bone (bone-DLBCL), including primary bone (PB-DLBCL, <i>n</i> = 52) and polyostotic-DLBCL (<i>n</i> = 20), in comparison to nodal DLBCLs with germinal center B-cell (GCB) phenotype (nodal-DLBCL-GCB, <i>n</i> = 34). PB-DLBCL and polyostotic-DLBCL shared similar genomic profiles and transcriptomic signatures, justifying their collective analysis as bone-DLBCL. Differential incidences of <i>EZH2</i>, <i>HIST1H1E</i>, and <i>MYC</i> aberrations (<i>p</i> < 0.05) confirmed the distinct oncogenic evolution between bone-DLBCL and nodal-DLBCL-GCB. Differentially expressed genes were identified between bone-DLBCL and nodal-DLBCL-GCB (<i>p</i> < 0.001), substantiated by distinct gene-set enrichment analysis (GSEA). In contrast to a more ‘depleted’ phenotype for nodal-DLBCL-GCB, bone-DLBCL primarily exhibited an ‘intermediate/rich’ tumor microenvironment (TME) signature (<i>p</i> = 0.001), as determined by a previously published gene set. Unsupervised clustering defined two distinct groups that aligned with previously reported immune-enriched TME clusters: an ‘immune-rich’ cluster largely consisting of bone-DLBCLs (75%, <i>p</i> = 0.002) with superior survival (<i>p</i> = 0.030), and a poor-prognostic ‘immune-low’ cluster, including mostly nodal-DLBCL-GCB (61%). Single-sample (ss)GSEA showed higher scores for regulatory T cells, immunosuppressive/prolymphoma cytokines, and vascular endothelial cells in immune-rich samples (<i>p</i> < 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (<i>p</i> < 0.001). These findings were confirmed at protein level, where CD3 and FOXP3 immunochemistry showed significant overlap with the gene-expression data (<i>p</i> < 0.001). Conclusively, PB-DLBCL and polyostotic-DLBCL share immune-molecular TME characteristics, supporting their classification as a unified bone-DLBCL entity. The distinct immune-rich TME profile of bone-DLBCL associated with superior survival potentially shapes emerging immunomodulatory strategies</p><figure></figure>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"46 12 1","pages":""},"PeriodicalIF":12.9000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment\",\"authors\":\"Ruben A. L. de Groen, Fleur A. de Groot, Stefan Böhringer, Esther J. 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In contrast to a more ‘depleted’ phenotype for nodal-DLBCL-GCB, bone-DLBCL primarily exhibited an ‘intermediate/rich’ tumor microenvironment (TME) signature (<i>p</i> = 0.001), as determined by a previously published gene set. Unsupervised clustering defined two distinct groups that aligned with previously reported immune-enriched TME clusters: an ‘immune-rich’ cluster largely consisting of bone-DLBCLs (75%, <i>p</i> = 0.002) with superior survival (<i>p</i> = 0.030), and a poor-prognostic ‘immune-low’ cluster, including mostly nodal-DLBCL-GCB (61%). Single-sample (ss)GSEA showed higher scores for regulatory T cells, immunosuppressive/prolymphoma cytokines, and vascular endothelial cells in immune-rich samples (<i>p</i> < 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (<i>p</i> < 0.001). 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Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment
With tumor genomic and gene-expression profiling (GEP), this study investigated the immune-molecular signatures of a unique cohort of diffuse large B-cell lymphoma of the bone (bone-DLBCL), including primary bone (PB-DLBCL, n = 52) and polyostotic-DLBCL (n = 20), in comparison to nodal DLBCLs with germinal center B-cell (GCB) phenotype (nodal-DLBCL-GCB, n = 34). PB-DLBCL and polyostotic-DLBCL shared similar genomic profiles and transcriptomic signatures, justifying their collective analysis as bone-DLBCL. Differential incidences of EZH2, HIST1H1E, and MYC aberrations (p < 0.05) confirmed the distinct oncogenic evolution between bone-DLBCL and nodal-DLBCL-GCB. Differentially expressed genes were identified between bone-DLBCL and nodal-DLBCL-GCB (p < 0.001), substantiated by distinct gene-set enrichment analysis (GSEA). In contrast to a more ‘depleted’ phenotype for nodal-DLBCL-GCB, bone-DLBCL primarily exhibited an ‘intermediate/rich’ tumor microenvironment (TME) signature (p = 0.001), as determined by a previously published gene set. Unsupervised clustering defined two distinct groups that aligned with previously reported immune-enriched TME clusters: an ‘immune-rich’ cluster largely consisting of bone-DLBCLs (75%, p = 0.002) with superior survival (p = 0.030), and a poor-prognostic ‘immune-low’ cluster, including mostly nodal-DLBCL-GCB (61%). Single-sample (ss)GSEA showed higher scores for regulatory T cells, immunosuppressive/prolymphoma cytokines, and vascular endothelial cells in immune-rich samples (p < 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (p < 0.001). These findings were confirmed at protein level, where CD3 and FOXP3 immunochemistry showed significant overlap with the gene-expression data (p < 0.001). Conclusively, PB-DLBCL and polyostotic-DLBCL share immune-molecular TME characteristics, supporting their classification as a unified bone-DLBCL entity. The distinct immune-rich TME profile of bone-DLBCL associated with superior survival potentially shapes emerging immunomodulatory strategies
期刊介绍：
Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as:
Preclinical studies of new compounds, especially those that provide mechanistic insights
Clinical trials and observations
Reviews related to new drugs and current management of hematologic malignancies
Novel observations related to new mutations, molecular pathways, and tumor genomics
Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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