ArticleBioMed research international2014
Lenalidomide induces immunomodulation in chronic lymphocytic leukemia and enhances antitumor immune responses mediated by NK and CD4 T cells.
Article in BioMed research international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis.Current oncology (Toronto, Ont.) · 2022Pooled it
- A phase 1/2 study of lenalidomide and obinutuzumab with CHOP for newly diagnosed DLBCL.Blood advances · 2023Trial
- Lack of impact of type and extent of prior therapy on outcomes of mogamulizumab therapy in patients with cutaneous T cell lymphoma in the MAVORIC trial.Leukemia & lymphoma · 2021Trial
- Efficacy and predictors of response of lenalidomide and rituximab in patients with treatment-naive and relapsed CLL.Blood advances · 2019Trial
- Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2018Trial
- Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.Cancer immunology, immunotherapy : CII · 2017Trial
- Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab.Cancer immunology research · 2015Trial
- Combining lenalidomide with IL-2 family of cytokines enhances activating receptor and perforin/granzyme expression in NK cells.PloS one · 2026Article
- Maintenance therapy for chronic lymphocytic leukaemia.The Cochrane database of systematic reviews · 2024Review
- Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era.Pharmaceutics · 2023Review
- Expanded natural killer cells potentiate the antimyeloma activity of daratumumab, lenalidomide, and dexamethasone in a myeloma xenograft model.Cancer immunology, immunotherapy : CII · 2023Article
- Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential.Cancers · 2022Review
- Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms.Frontiers in immunology · 2022Review
- Immunomodulatory Drugs for the Treatment of B Cell Malignancies.International journal of molecular sciences · 2021Review
- LAG-3 Blockade with Relatlimab (BMS-986016) Restores Anti-Leukemic Responses in Chronic Lymphocytic Leukemia.Cancers · 2021Article
- Intrinsic Resistance of Chronic Lymphocytic Leukemia Cells to NK Cell-Mediated Lysis Can Be OvercomeFrontiers in immunology · 2021Article
- Mechanisms of Resistance to NK Cell Immunotherapy.Cancers · 2020Review
- Review
- NK Cells in the Treatment of Hematological Malignancies.Journal of clinical medicine · 2019Review
- Sustained long-lasting responses after lenalidomide discontinuation in patients with chronic lymphocytic leukemia.Leukemia · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lenalidomide is an immunomodulatory drug with therapeutic activity in chronic lymphocytic leukemia (CLL). However, it has pleiotropic effects, and the mechanism of action responsible for its therapeutic activity has not been well defined yet. Herein, we show that lenalidomide treatment does not have an effect on the proliferation of leukemia cells, but it increases the proliferation of B cells from healthy donors. Lenalidomide did not exert a direct effect on the apoptosis of leukemia cells obtained from CLL patients, although it indirectly induced their apoptosis through the activation of nonmalignant immune cells. Thus, lenalidomide markedly increased the proliferation of NK and CD4 T cells. The effect of lenalidomide on NK cells was secondary to the induction of IL-2 production by CD4 T cells. Accordingly, depletion of T cells or blockade of IL-2 activity completely abrogated the proliferation of NK cells. Additionally, lenalidomide enhanced NK and NKT-like cell-mediated natural cytotoxicity against leukemia cells from CLL patients. Lenalidomide also upregulated CD20 expression on leukemia cells and, accordingly, it had a synergistic effect with rituximab on promoting antibody-dependent cell-mediated cytotoxicity against primary leukemia cells. Overall, these observations provide a support for combining lenalidomide with rituximab as a treatment in CLL.
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