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<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> &lt; 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> &lt; 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> &lt; 0.001). Additionally, CIBERSORTx revealed a higher abundance of regulatory T cells and activated mast cells in the immune-rich cluster (<i>p</i> &lt; 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> &lt; 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><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月29日

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  • 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

摘要

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