Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 39–49

Lenalidomide enhances anti-myeloma cellular immunity

  • 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
Original article

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.

Keywords

Lenalidomide Multiple myeloma Dendritic cell vaccine PD-1 

Supplementary material

262_2012_1308_MOESM1_ESM.ppt (116 kb)
Supplementary material 1 (PPT 115 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Katarina Luptakova
    • 1
  • Jacalyn Rosenblatt
    • 1
  • Brett Glotzbecker
    • 2
  • Heidi Mills
    • 1
  • Dina Stroopinsky
    • 1
  • Turner Kufe
    • 1
  • Baldev Vasir
    • 2
  • Jon Arnason
    • 1
  • Dimitri Tzachanis
    • 1
  • Jeffrey I. Zwicker
    • 1
  • Robin M. Joyce
    • 1
  • James D. Levine
    • 1
  • Kenneth C. Anderson
    • 2
  • Donald Kufe
    • 2
  • David Avigan
    • 1
  1. 1.Division of Hematology/OncologyBeth Israel Deaconess Medical CenterBostonUSA
  2. 2.Dana Farber Cancer InstituteBostonUSA

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