ArticleJournal for immunotherapy of cancer2019
Immunoglobulin somatic hypermutation has clinical impact in DLBCL and potential implications for immune checkpoint blockade and neoantigen-based immunotherapies.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Article
- Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Tutorial: integrative computational analysis of bulk RNA-sequencing data to characterize tumor immunity using RIMA.Nature protocols · 2023Review
- The Immunology of DLBCL.Cancers · 2023Review
- Extracellular Vesicles in Diffuse Large B Cell Lymphoma: Characterization and Diagnostic Potential.International journal of molecular sciences · 2022Article
- Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside.Experimental hematology & oncology · 2022Review
- Benchmarking computational methods for B-cell receptor reconstruction from single-cell RNA-seq data.NAR genomics and bioinformatics · 2022Article
- Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin lymphomas: frequency, genetic mechanisms, and clinical significance.Haematologica · 2022Article
- Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV.Frontiers in oncology · 2022Article
- Article
- Article
- Recurrence Risk of Liver Cancer Post-hepatectomy Using Machine Learning and Study of Correlation With Immune Infiltration.Frontiers in genetics · 2021Article
- Genomic complexity is associated with epigenetic regulator mutations and poor prognosis in diffuse large B-cell lymphoma.Oncoimmunology · 2021Article
- Therapeutic vaccines for aggressive B-cell lymphoma.Leukemia & lymphoma · 2020Article
- Chemotherapy Curability in Leukemia, Lymphoma, Germ Cell Tumors and Gestational Malignancies: A Reflection of the Unique Physiology of Their Cells of Origin.Frontiers in genetics · 2020Article
- CD4Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
30 authors at 19 institutions in 8 countries.
Funding
Abstract
backgroundDiffuse large B-cell lymphoma (DLBCL) harbors somatic hypermutation (SHM) in the immunoglobulin heavy chain and light chain variable region genes, IGHV and IGK/LV. Recent studies have revealed that IGV SHM creates neoantigens that activate T-cell responses against B-cell lymphoma.
methodsTo determine the clinical relevance of IGV SHM in DLBCL treated with standard immunochemotherapy, we performed next-generation sequencing of the immunoglobulin variable regions and complementarity determining region 3 (CDR3) for 378 patients with de novo DLBCL. The prognostic effects of IGV SHM and ongoing SHM or intra-clonal heterogeneity were analyzed in the training (192 patients), validation (186 patients), and overall DLBCL cohorts. To gain mechanistic insight, we analyzed the predicted IG-derived neoantigens' immunogenicity potential, determined by the major histocompatibility complex-binding affinity and the frequency-of-occurrence of T cell-exposed motifs (TCEMs) in a TCEM repertoire derived from human proteome, microbiome, and pathogen databases. Furthermore, IGV SHM was correlated with molecular characteristics of DLBCL and PD-1/L1 expression in the tumor microenvironment assessed by fluorescent multiplex immunohistochemistry.
resultsSHM was commonly found in IGHV and less frequently in IGK/LV. High levels of clonal IGHV SHM (SHM
conclusionsThese results show for the first time that IGV SHM
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