TY - JOUR
T1 - Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment
AU - de Groen, Ruben A.L.
AU - de Groot, Fleur A.
AU - Böhringer, Stefan
AU - Kret, Esther J.
AU - de Haan, Lorraine M.
AU - Noordenbos, Troy
AU - Blommers, Susan
AU - Jansen, Romée E.W.
AU - van Wezel, Tom
AU - van Eijk, Ronald
AU - Raghoo, Richard
AU - Ruano, Dina
AU - Boome, Liane te
AU - Terpstra, Valeska
AU - Levenga, Henriette
AU - Ahsmann, Els
AU - Posthuma, Eduardus F.M.
AU - Focke-Snieders, Isabelle
AU - Hardi, Lizan
AU - den Hartog, Wietske C.E.
AU - van den Berg, Anke
AU - Mutsaers, Pim
AU - Lam, King
AU - van der Poel, Marjolein W.M.
AU - Hamid, Myrurgia Abdul
AU - Woei-A-Jin, F. J.Sherida H.
AU - Janssens, Ann
AU - Tousseyn, Thomas
AU - Bovée, Judith V.M.G.
AU - Koens, Lianne
AU - Diepstra, Arjan
AU - Cleven, Arjen H.G.
AU - Kersten, Marie José
AU - Jansen, Patty M.
AU - Veelken, Hendrik
AU - Nijland, Marcel
AU - Dekker, Tim J.A.
AU - Vermaat, Joost S.P.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/4/29
Y1 - 2025/4/29
N2 - 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 (Figure presented.)
AB - 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 (Figure presented.)
UR - https://www.scopus.com/pages/publications/105003863407
U2 - 10.1038/s41408-025-01291-z
DO - 10.1038/s41408-025-01291-z
M3 - Article
C2 - 40301298
AN - SCOPUS:105003863407
SN - 2044-5385
VL - 15
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 1
M1 - 82
ER -