ArticleNature communications2022
Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Integrated Transcriptomic Analysis ofInternational journal of molecular sciences · 2026Article
- DNMT2-m5C-ACLY Axis Promotes Lenvatinib Resistance in Hepatocellular Carcinoma Through Histone Acetylation-Mediated Notch Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Facilitating Gene Editing in Human Lymphoma Cells Using Murine Ecotropic γ-Retroviruses.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Genetic Manipulation and Extended Culture of Human Germinal Center B Cells to Model Lymphomagenesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Adoptive cell therapy against tumor immune evasion: mechanisms, innovations, and future directions.Frontiers in oncology · 2025Review
- Notch pathway inhibition with crenigacestat (LY3039478) in a phase I first-in-human clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia.Therapeutic advances in drug safety · 2025Article
- CRTC1 enhances PD-L1-mediated tumor immunosuppression in non-small cell lung cancer via the Notch1/Akt signaling pathway.Frontiers in immunology · 2025Article
- NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia.Leukemia · 2024Article
- Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma.Cell death & disease · 2024Article
- Molecular Subtypes and the Role of TP53 in Diffuse Large B-Cell Lymphoma and Richter Syndrome.Cancers · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- GHITM regulates malignant phenotype and sensitivity to PD-1 blockade of renal cancer cells via Notch signalling.Journal of cellular and molecular medicine · 2024Article
- Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.Journal of clinical and experimental hematopathology : JCEH · 2024Article
- ZAP-70 augments tonic B-cell receptor and CCR7 signaling in IGHV-unmutated chronic lymphocytic leukemia.Blood advances · 2024Article
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- Integrated genetic analyses of immunodeficiency-associated Epstein-Barr virus- (EBV) positive primary CNS lymphomas.Acta neuropathologica · 2023Article
- Robust CRISPR-Cas9 Genetic Editing of Primary Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma Cells.HemaSphere · 2023Article
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified in B cell malignancies. To address how NOTCH-mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of the intracellular domain (ICD) of NOTCH1 or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-γ signaling. In addition, NOTCH-activation causes silencing of the entire HLA-class II locus via epigenetic regulation of the transcriptional co-activator CIITA. Notably, while NOTCH1 and NOTCH2 govern similar transcriptional programs, disease-specific differences in their expression levels can favor paralog-specific selection. Importantly, NOTCH-ICD also strongly down-regulates the expression of CD19, possibly limiting the effectiveness of immune-therapies. These NOTCH-mediated immune escape mechanisms are associated with the expansion of exhausted CD8
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Registered trials
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