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Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis

AuthorsPaiva, Bruno; Mateos, Maria Victoria; Sánchez-Abarca, Luis Ignacio; Puig, Noemi; Vidriales, Maria Belén ; López-Corral, L.; Corchete, Luis A.; Hernandez, Miguel T.; Bargay, Joan; Arriba, Felipe de; Rubia, Javier de la; Teruel, Ana-Isabel; Giraldo, Pilar; Rosiñol, Laura; Prosper, Felipe; Oriol, Albert; Hernández, José ; Esteves, Graça; Lahuerta, Juan José; Bladé, Joan; Pérez-Simón, José A.; San Miguel, Jesús F.
Issue Date2016
PublisherAmerican Society of Hematology
CitationBlood 127(9): 1151-1162 (2016)
AbstractThere is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor γδ, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High-risk SMM patients showed at baseline decreased expression of activation-(CD25/CD28/CD54), type 1 T helper-(CD195/interferon-γ/tumor necrosis factor-α/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma.
DescriptionOn behalf of the Grupo Español de Mieloma/Programa de Estudio y Tratamiento de las Hemopatías Malignas cooperative study groups.
Identifiersdoi: 10.1182/blood-2015-10-662320
issn: 0006-4971
e-issn: 1528-0020
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