Characterisation of immune checkpoints in Richter syndrome identifies LAG3 as a potential therapeutic target
| Autor: | Costas K. Yannakou, John F. Seymour, John F. Markham, Michael Dickinson, Stephen Lade, Jennifer Lickiss, Paul J Neeson, Piers Blombery, Diego Villa, Satwica Yerneni, David Westerman, Collin K. Chin, Yamuna Kankanige, Constantine S. Tam, Graham W. Slack, Clare Gould, Niles Elizabeth Nelson, Maher K. Gandhi |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
LAG3 DNA Copy Number Variations Context (language use) Aggressive lymphoma Lymphocytes Tumor-Infiltrating Immune system Antigens CD Internal medicine Humans Medicine Molecular Targeted Therapy Immune Checkpoint Inhibitors Lymphoma Follicular B-Lymphocytes Hematology business.industry Gene Expression Profiling Lymphoma B-Cell Marginal Zone Syndrome medicine.disease Leukemia Lymphocytic Chronic B-Cell Lymphocyte Activation Gene 3 Protein Immune checkpoint Neoplasm Proteins Lymphoma Gene expression profiling Disease Progression Neoplastic Stem Cells Cancer research Lymphoma Large B-Cell Diffuse business |
| Zdroj: | British Journal of Haematology. 195:113-118 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/bjh.17789 |
| Popis: | Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B-cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS. Formalin-fixed, paraffin-embedded biopsies of RS (n = 19), de novo diffuse large B-cell lymphoma (DLBCL; n = 58), transformed indolent lymphomas (follicular [tFL], n = 16; marginal zone [tMZL], n = 24) and non-transformed small lymphocytic lymphoma (SLL; n = 15) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next-generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD-1 was performed. LAG3 gene expression was higher in RS compared to DLBCL (P = 0·0002, log2FC 1·96), tFL (P |
| Databáze: | OpenAIRE |
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