Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications.
Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Pharmacologic approaches to enhance NKT cell function will facilitate specific NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel thalidomide (Thal) analog, enhances antigen-specific expansion of NKT cells in response to the NKT ligand alpha-galactosylceramide (alpha-GalCer) in both healthy donors and patients with myeloma. NKT cells activated in the presence of LEN have greater ability to secrete interferon-gamma. Antigen-dependent activation of NKT cells was greater in the presence of dexamethasone (DEX) plus LEN than with DEX alone. Therapy with LEN/Thal also led to an increase in NKT cells in vivo in patients with myeloma and del5q myelodysplastic syndrome. Together these data demonstrate that LEN and its analogues enhance CD1d-mediated presentation of glycolipid antigens and support combining these agents with NKT targeted approaches for protection against tumors.
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
David H
DH
Chang
Nancy
N
Liu
Virginia
V
Klimek
Hani
H
Hassoun
Amitabha
A
Mazumder
Stephen D
SD
Nimer
Sundar
S
Jagannath
Madhav V
MV
Dhodapkar
D017951:Antigen Presentation / Q000187:drug effects; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D000077269:Lenalidomide; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects*; D009101:Multiple Myeloma / Q000276:immunology; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D005699:Galactosylceramides; D008024:Ligands; C493154:alpha-galactosylceramide; D013792:Thalidomide; D000077269:Lenalidomide