Lenalidomide enhances anti-myeloma cellular immunity.
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.
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. kluptako@bidmc.harvard.edu
Katarina
K
Luptakova
Jacalyn
J
Rosenblatt
Brett
B
Glotzbecker
Heidi
H
Mills
Dina
D
Stroopinsky
Turner
T
Kufe
Baldev
B
Vasir
Jon
J
Arnason
Dimitri
D
Tzachanis
Jeffrey I
JI
Zwicker
Robin M
RM
Joyce
James D
JD
Levine
Kenneth C
KC
Anderson
Donald
D
Kufe
David
D
Avigan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D015151:Immunoblotting; D000077269:Lenalidomide; D008213:Lymphocyte Activation / Q000187:drug effects; D009101:Multiple Myeloma / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D013792:Thalidomide; D000077269:Lenalidomide