Troy Noordenbos

All Publications

• Superior survival in diffuse large B cell lymphoma of the bone with immune rich tumor microenvironment. Blood cancer journal de Groen, R. A., de Groot, F. A., Böhringer, S., Kret, E. J., de Haan, L. M., Noordenbos, T., Blommers, S., Jansen, R. E., van Wezel, T., van Eijk, R., Raghoo, R., Ruano, D., Boome, L. T., Terpstra, V., Levenga, H., Ahsmann, E., Posthuma, E. F., Focke-Snieders, I., Hardi, L., den Hartog, W. C., van den Berg, A., Mutsaers, P., Lam, K., van der Poel, M. W., Hamid, M. A., Woei-A-Jin, F. J., Janssens, A., Tousseyn, T., Bovée, J. V., Koens, L., Diepstra, A., Cleven, A. H., Kersten, M. J., Jansen, P. M., Veelken, H., Nijland, M., Dekker, T. J., Vermaat, J. S. 2025; 15 (1): 82

  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.

  View details for DOI 10.1038/s41408-025-01291-z

  View details for PubMedID 40301298

  View details for PubMedCentralID 3958453

• Distinct Molecular Aberrations of Classic Hodgkin Lymphoma in Older Adults Identified By Comprehensive Genomic Profiling Rossi, C., Boegeholz, J., Goldstein, J. S., Shi, S., Su, S., Tessoulin, B., Alig, S. K., Garofalo, A., Esfahani, M., Schroers-Martin, J. G., Liu, C., Olsen, M., Kang, X., Tian, F., Kurtz, D., Sugio, T., Noordenbos, T., Andre, M., Fornecker, L., Julia, E., Traverse-Glehen, A., Casasnovas, O., Binkley, M. S., Diehn, M., Ghesquieres, H., Alizadeh, A. A. ELSEVIER. 2024: 853-854

  View details for DOI 10.1182/blood-2024-201644

  View details for Web of Science ID 001412608600046

• Integrating Genomic & Transcriptomic Features for Noninvasive Detection, Characterization, and Monitoring of T-Cell Lymphomas Sugio, T., Nesselbush, M., Shukla, N., Garofalo, A., Mutter, J. A., Esfahani, M., Alig, S. K., Shi, S., Noordenbos, T., Hamilton, M. P., Rossi, C., Tian, F., Liu, C., Olsen, M., Kang, X., Russler-Germain, D. A., Horwitz, S., Kato, K., Ito, A., Yamagishi, M., Fukuda, T., Akashi, K., Uchimaru, K., Khodadoust, M. S., Diehn, M., Mehta-Shah, N., Alizadeh, A. A. ELSEVIER. 2024: 454-455

  View details for DOI 10.1182/blood-2024-206518

  View details for Web of Science ID 001415654100004

• Resolving the Microarchitecture of Classic and Transformed Follicular Lymphoma By Single Cell Alignment to Spatial Transcriptomes Noordenbos, T., Schroers-Martin, J. G., Hamilton, M. P., Jun, S., Sugio, T., Sworder, B. J., Steen, C., Olsen, M., Liu, C., Newman, A., Howitt, B., Natkunam, Y., Miklos, D. B., Diehn, M., Frank, M. J., Alizadeh, A. A. ELSEVIER. 2024: 2993-2994

  View details for DOI 10.1182/blood-2024-199300

  View details for Web of Science ID 001412630600038

• Immunosuppressed Tumor Microenvironment in <i>MYC</i>-Rearranged High-Grade B-Cell Lymphomas Compared to Diffuse Large B-Cell Lymphomas, Not Otherwise Specified De Jonge, A., Noordenbos, T., De Groen, R. L., De Groot, F. A., De Haan-Treurniet, L. M., Jansen, P. M., Fu, L., de Heer, K., Klerk, C., Sandberg, Y., Fijnheer, R., Mutsaers, P., Beeker, A., Bohmer, L. H., Wang, S., Strobbe, L., Boersma, R., Oosterveld, M., Koene, H. R., De Miranda, N., van den Berg, A., Nijland, M., Roemer, M. M., Mutis, T., Chamuleau, M. D., Vermaat, J. P. ELSEVIER. 2024: 4380-4381

  View details for DOI 10.1182/blood-2024-205968

  View details for Web of Science ID 001409330600015

• Comprehensive Characterization of the Cell States and Ecosystems in Classic Hodgkin Lymphoma Using Single-Cell RNA-Seq, Digital Deconvolution, and Machine Learning Su, S., Subramanian, A., Flerlage, T., Flerlage, J. E., Rossi, C., Noordenbos, T., Schroers-Martin, J. G., Moding, E. J., Hoppe, R. T., Advani, R. H., Natkunam, Y., Alizadeh, A. A., Binkley, M. S. ELSEVIER. 2024: 4369-4370

  View details for DOI 10.1182/blood-2024-212013

  View details for Web of Science ID 001409330600004

• Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy. The New England journal of medicine Hamilton, M. P., Sugio, T., Noordenbos, T., Shi, S., Bulterys, P. L., Liu, C. L., Kang, X., Olsen, M. N., Good, Z., Dahiya, S., Frank, M. J., Sahaf, B., Mackall, C. L., Gratzinger, D., Diehn, M., Alizadeh, A. A., Miklos, D. B. 2024; 390 (22): 2047-2060

  Abstract

  The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern.We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR T cells, and the normal hematopoietic cells in the patient.A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques.Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).

  View details for DOI 10.1056/NEJMoa2401361

  View details for PubMedID 38865660