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.

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Publication Details

Journal
Blood Cancer Journal
Published
2025-04-29
DOI
https://doi.org/10.1038/s41408-025-01291-z
Citations
4
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
5.89

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article

Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment

Lizan Hardi, Anke van den Berg, Lorraine M. de Haan, Fleur A. de Groot et al.
4 citations
Blood Cancer Journal
Lymphoma Diagnosis and Treatment
5.89
article

Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment

Lizan Hardi, Anke van den Berg, Lorraine M. de Haan, Fleur A. de Groot, Slinger Jansen, Eduardus F. M. Posthuma, Troy Noordenbos, Marcel Nijland, Esther J Kret, Pim G. N. J. Mutsaers, Wietske C. E. den Hartog, Tom van Wezel, Ronald van Eijk, Marie José Kersten, Dina Ruano, Els Ahsmann, Lianne Koens, Valeska Terpstra, Liane te Boome, Tim Dekker, Isabelle Focke‐Snieders, King H. Lam, Hendrik Veelken, Henriëtte Levenga, Patty M. Jansen, Joost S.P. Vermaat, Ann Janssens, Feng Jung Sherida H. Woei-A-Jin, Stefan Böhringer, Judith V.M.G. Bovée, Arjan Diepstra, Arjen H.G. Cleven, Thomas Tousseyn, Richard Raghoo, Ruben A. L. de Groen, Marjolein W.M. van der Poel, Myrurgia Abdul Hamid, Susan Blommers
article en
4 citations

Abstract

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.

Blood Cancer JournalVol. 15(1)
University Medical Center Groningen (NL), University of Groningen (NL), Leiden University Medical Center (NL), Maastricht University (NL), Medisch Centrum Haaglanden (NL), Reinier de Graaf Hospital (NL), Alrijne Ziekenhuis (NL), Groene Hart Ziekenhuis (NL), Erasmus MC Cancer Institute (NL), Amsterdam University Medical Centers (NL), Cancer Center Amsterdam (NL), University of Amsterdam (NL), Stanford University (US), KU Leuven (BE)
National Institutes of Health, National Cancer Institute
Zero hunger
Openalex Percentile: Top 4%
Lymphoma Diagnosis and Treatment
5.89
DOIOpen Access PDFOpenAlex
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