Lenalidomide combined with low-dose cyclophosphamide and prednisone modulates Ikaros and Aiolos in lymphocytes, resulting in immunostimulatory effects in lenalidomide-refractory multiple myeloma patients
| العنوان: | Lenalidomide combined with low-dose cyclophosphamide and prednisone modulates Ikaros and Aiolos in lymphocytes, resulting in immunostimulatory effects in lenalidomide-refractory multiple myeloma patients |
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| المؤلفون: | Ellen van der Spek, Laurens E. Franssen, Pieter Sonneveld, Laura M. Faber, Xiaozhong Qian, Ruud Doorn, Anjan Thakurta, Gerard M. J. Bos, Sonja Zweegman, Jeroen F. van Velzen, Henk M. Lokhorst, Hsiling Chiu, Saskia K. Klein, Berris van Kessel, Inger S. Nijhof, Harry R. Koene, Maarten Emmelot, Reinier Raymakers, Niels W.C.J. van de Donk, Tuna Mutis, Andries C. Bloem, Chad C. Bjorklund, Mark-David Levin, Annemiek Broijl, Aart Beeker |
| المساهمون: | Hematology laboratory, Internal medicine, Hematology, CCA - Cancer biology and immunology, AII - Cancer immunology |
| المصدر: | Oncotarget, 9(74), 34009-34021. Impact Journals Franssen, L E, Nijhof, I S, Bjorklund, C C, Chiu, H, Doorn, R, Van Velzen, J, Emmelot, M, Van Kessel, B, Levin, M D, Bos, G M J, Broijl, A, Klein, S K, Koene, H R, Bloem, A C, Beeker, A, Faber, L M, Van Der Spek, E, Raymakers, R, Sonneveld, P, Zweegman, S, Lokhorst, H M, Thakurta, A, Qian, X, Mutis, T & Van De Donk, N W C J 2018, ' Lenalidomide combined with low-dose cyclophosphamide and prednisone modulates Ikaros and Aiolos in lymphocytes, resulting in immunostimulatory effects in lenalidomide-refractory multiple myeloma patients ', Oncotarget, vol. 9, no. 74, pp. 34009-34021 . Oncotarget Oncotarget, 9(74), 34009-34021. Impact Journals LLC Oncotarget, 9(74), 34009. Impact Journals |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Cyclophosphamide, lenalidomide, Pharmacology, Plasma cell, immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, Prednisone, medicine, Multiple myeloma, Lenalidomide, business.industry, Cereblon, medicine.disease, In vitro, multiple myeloma, refractory, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, cyclophosphamide, business, 030215 immunology, medicine.drug, Research Paper |
| الوصف: | We recently showed that the outcome of multiple myeloma (MM) patients treated in the REPEAT study (evaluation of lenalidomide combined with low-dose cyclophosphamide and prednisone (REP) in lenalidomide-refractory MM) was markedly better than what has been described with cyclophosphamide-prednisone alone. The outcome with REP was not associated with plasma cell Cereblon expression levels, suggesting that the effect of REP treatment may involve mechanisms independent of plasma cell Cereblon-mediated direct anti-tumor activity. We therefore hypothesized that immunomodulatory effects contribute to the anti-MM activity of REP treatment, rather than plasma cell Cereblon-mediated effects. Consequently, we now characterized the effect of REP treatment on immune cell subsets in peripheral blood samples collected on day 1 and 14 of cycle 1, as well as on day 1 of cycle 2. We observed a significant mid-cycle decrease in the Cereblon substrate proteins Ikaros and Aiolos in diverse lymphocyte subsets, which was paralleled by an increase in T-cell activation. These effects were restored to baseline at day one of the second cycle, one week after lenalidomide interruption. In vitro, lenalidomide enhanced peripheral blood mononuclear cell-mediated killing of both lenalidomide-sensitive and lenalidomide-resistant MM cells in a co-culture system. These results indicate that the Cereblon-mediated immunomodulatory properties of lenalidomide are maintained in lenalidomide-refractory MM patients and may contribute to immune-mediated killing of MM cells. Therefore, combining lenalidomide with other drugs can have potent effects through immunomodulation, even in patients considered to be lenalidomide-refractory. |
| وصف الملف: | image/pdf |
| اللغة: | English |
| تدمد: | 1949-2553 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e4e05171aec04316e7150137f39e01b5 https://research.vumc.nl/en/publications/9952d8a0-3eca-4554-a20a-1f5c0b426190 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e4e05171aec04316e7150137f39e01b5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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