title: Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation.
abstract: Multiple myeloma (MM) is characterized by a malignant proliferation of plasma cells in the bone marrow with associated organ damage. Although the prognosis of MM has improved recently, the disease remains incurable for the large majority of patients. The eradication of residual disease in the bone marrow is a main target on the road toward cure. Immune cells play a role in the control of cancer and can be tools to attack residual MM cells. However, the myeloma-associated immune deficiency is a major hurdle to immunotherapy. We evaluated ex vivo the effects of low doses of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide on several immune cell types from MM patients after autologous stem cell transplantation and with low tumor burden. We observed that these drugs increased CD4(+) and CD8(+) T-cell proliferation and cytokine production, enhanced the lytic capacity of cytotoxic T lymphocytes and reduced the suppressive effects of regulatory T cells on CD8(+) T-cell responses. In addition, we found that functional dendritic cells (DCs) can be generated from mononuclear cells from MM patients. The presence of IMiDs improved the quality of antigen-specific T cells induced or expanded by these DCs as evidenced by a higher degree of T-cell polyfunctionality. Our results provide a rationale for the design of early phase clinical studies to assess the efficacy of DC-based immunotherapy in combination with posttransplant maintenance treatment with IMiDs in MM.
authors.affiliation: Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium, bdekeers@vub.ac.be.
authors.forename: Brenda
authors.initials: B
authors.lastname: De Keersmaecker
authors.forename: Karel
authors.initials: K
authors.lastname: Fostier
authors.forename: Jurgen
authors.initials: J
authors.lastname: Corthals
authors.forename: Sofie
authors.initials: S
authors.lastname: Wilgenhof
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Joeri L
authors.initials: JL
authors.lastname: Aerts
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Rik
authors.initials: R
authors.lastname: Schots
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D056747:Immunomodulation; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D020533:Angiogenesis Inhibitors; D007155:Immunologic Factors; D013792:Thalidomide; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; C467566:pomalidomide; D000077269:Lenalidomide; D008558:Melphalan