Lenalidomide enhances anti-myeloma cellular immunity |
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Authors: | Katarina Luptakova Jacalyn Rosenblatt Brett Glotzbecker Heidi Mills Dina Stroopinsky Turner Kufe Baldev Vasir Jon Arnason Dimitri Tzachanis Jeffrey I Zwicker Robin M Joyce James D Levine Kenneth C Anderson Donald Kufe David Avigan |
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Institution: | 1. Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA, 02215, USA 2. Dana Farber Cancer Institute, Boston, MA, USA
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Abstract: | Lenalidomide is an effective therapeutic agent for multiple myeloma that exhibits immunomodulatory properties including the activation of T and NK cells. The use of lenalidomide to reverse tumor-mediated immune suppression and amplify myeloma-specific immunity is currently being explored. In the present study, we examined the effect of lenalidomide on T-cell activation and its ability to amplify responses to a dendritic cell-based myeloma vaccine. We demonstrate that exposure to lenalidomide in the context of T-cell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFN-γ, but not IL-10 expression. In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a decrease in T-cell expression of the inhibitory marker, PD-1. Lenalidomide also enhanced T-cell proliferative responses to allogeneic DCs. Most significantly, lenalidomide treatment potentiated responses to the dendritic cell/myeloma fusion vaccine, which were characterized by increased production of inflammatory cytokines and increased cytotoxic lymphocyte-mediated lysis of autologous myeloma targets. These findings indicate that lenalidomide enhances the immunologic milieu in patients with myeloma by promoting T-cell proliferation and suppressing inhibitory factors, and thereby augmenting responses to a myeloma-specific tumor vaccine. |
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