ArticleBlood advances2020
Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Regulating the regulators via targeting CD38 in the tumor microenvironment.Frontiers in immunology · 2026Review
- Single-cell dissection of hepatocellular carcinoma immunity: from heterogeneous subtypes to precision therapeutics.Frontiers in immunology · 2026Review
- One tool, multiple gains: anti-CD38 therapy in antibody-mediated rejection.Clinical kidney journal · 2025Article
- Revealing the role of regulatory b cells in cancer: development, function and treatment significance.Cancer immunology, immunotherapy : CII · 2025Review
- Targeting T regulatory (TCancer drug resistance (Alhambra, Calif.) · 2024Review
- Immuno-regulatory malignant B cells contribute to Chronic Lymphocytic Leukemia progression.Cancer gene therapy · 2023Article
- The role of Th17 cells in chronic lymphocytic leukemia: friend or foe?Blood advances · 2023Review
- AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma.Cancers · 2023Article
- Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Chimeric Antigen Receptor T-cell Therapy for Chronic Lymphocytic Leukemia: What is the supporting evidence so far?Clinical hematology international · 2023Review
- Mechanisms of induction of regulatory B cells in the tumour microenvironment and their contribution to immunosuppression and pro-tumour responses.Clinical and experimental immunology · 2022Review
- Reprogramming the tumor microenvironment by genome editing for precision cancer therapy.Molecular cancer · 2022Review
- Identification of CD105 (endoglin) as novel risk marker in CLL.Annals of hematology · 2022Article
- The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.American journal of physiology. Cell physiology · 2022Review
- Regulatory T cells (Tregs) in lymphoid malignancies and the impact of novel therapies.Frontiers in immunology · 2022Review
- B cell-T cell interplay in immune regulation: A focus on follicular regulatory T and regulatory B cell functions.Frontiers in cell and developmental biology · 2022Review
- Targeting the tumor microenvironment in chronic lymphocytic leukemia.Haematologica · 2021Review
- Impact of Immune Parameters and Immune Dysfunctions on the Prognosis of Patients with Chronic Lymphocytic Leukemia.Cancers · 2021Review
- Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?Frontiers in immunology · 2021Article
- Immunosuppressive Mechanisms of Regulatory B Cells.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]-like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL-patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.
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