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
Publish Date: 2012/06/24
Volume: 62, Issue: 1, Pages: 39-49
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 tumormediated immune suppression and amplify myelomaspecific immunity is currently being explored In the present study we examined the effect of lenalidomide on Tcell activation and its ability to amplify responses to a dendritic cellbased myeloma vaccine We demonstrate that exposure to lenalidomide in the context of Tcell expansion with direct ligation of CD3/CD28 complex results in polarization toward a Th1 phenotype characterized by increased IFNγ but not IL10 expression In vitro exposure to lenalidomide resulted in decreased levels of regulatory T cells and a decrease in Tcell expression of the inhibitory marker PD1 Lenalidomide also enhanced Tcell 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 lymphocytemediated lysis of autologous myeloma targets These findings indicate that lenalidomide enhances the immunologic milieu in patients with myeloma by promoting Tcell proliferation and suppressing inhibitory factors and thereby augmenting responses to a myelomaspecific tumor vaccine
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