ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Article
- Proinflammatory GSDMD activation in live macrophages and DLBCL cells marks cognate interactions and better prognosis.Blood advances · 2026Article
- XBP1-driven proliferative B cell subcluster in Diffuse Large B Cell Lymphoma linked to altered nucleotide metabolism.European journal of medical research · 2026Article
- Review
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Practical microenvironment classification in diffuse large B cell lymphoma using digital pathology.Cell reports. Medicine · 2025Article
- Epigenetic Symphony in Diffuse Large B-Cell Lymphoma: Orchestrating the Tumor Microenvironment.Biomedicines · 2025Review
- Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5'RACE.Blood advances · 2025Article
- UBR5 in Tumor Biology: Exploring Mechanisms of Immune Regulation and Possible Therapeutic Implications in MPNST.Cancers · 2025Review
- Nutritional and immune-inflammatory scoring system for predicting outcomes in newly diagnosed diffuse large B-cell lymphoma patients.Frontiers in nutrition · 2025Article
- Single-cell RNA sequencing in diffuse large B-cell lymphoma: tumor heterogeneity, microenvironment, resistance, and prognostic markers.Frontiers in oncology · 2025Review
- Metabolic-immune axis in the tumor microenvironment: a new strategy for prognostic assessment and precision therapy in DLBCL and FL.Frontiers in immunology · 2025Review
- Targeting RAB7 in human B lymphoma by a small molecule inhibitor arrests tumor cell growth.Frontiers in oncology · 2025Article
- Unraveling the Immune Microenvironment in Diffuse Large B-Cell Lymphoma: Prognostic and Potential Therapeutic Implications.Current issues in molecular biology · 2024Review
- Review
- Commentary: Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma.Frontiers in immunology · 2024Article
- Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma.Frontiers in immunology · 2024Article
- DNA mismatch repair defect and intratumor heterogeneous deficiency differently impact immune responses in diffuse large B-cell lymphoma.Oncoimmunology · 2024Article
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Authors and funding
31 authors at 20 institutions in 8 countries.
Funding
Abstract
purposeTumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance. EXPERIMENTAL
designA total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution.
resultsTIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell-like/activated B-cell-like classification and TIL-T frequency. The identified TIL-B-high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts.
conclusionsTIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.
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