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Lenalidomide enhances anti-myeloma cellular immunity

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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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Acknowledgments

This study was supported by research funding from Celgene to J.R.

Conflict of interest

J.R. has received research funding from Celgene. K.C.A. is on the advisory board of Celgene. The remaining authors declare no competing conflicts of interest.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA, 02215, USA

    Katarina Luptakova, Jacalyn Rosenblatt, Heidi Mills, Dina Stroopinsky, Turner Kufe, Jon Arnason, Dimitri Tzachanis, Jeffrey I. Zwicker, Robin M. Joyce, James D. Levine & David Avigan

  2. Dana Farber Cancer Institute, Boston, MA, USA

    Brett Glotzbecker, Baldev Vasir, Kenneth C. Anderson & Donald Kufe

Authors
  1. Katarina Luptakova
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  2. Jacalyn Rosenblatt
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Correspondence to Katarina Luptakova.

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Luptakova, K., Rosenblatt, J., Glotzbecker, B. et al. Lenalidomide enhances anti-myeloma cellular immunity. Cancer Immunol Immunother 62, 39–49 (2013). https://doi.org/10.1007/s00262-012-1308-3

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  • DOI: https://doi.org/10.1007/s00262-012-1308-3

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