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Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications.
- Source :
-
Blood [Blood] 2006 Jul 15; Vol. 108 (2), pp. 618-21. Date of Electronic Publication: 2006 Mar 28. - Publication Year :
- 2006
-
Abstract
- 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.
- Subjects :
- Antigen Presentation drug effects
Cells, Cultured
Galactosylceramides pharmacology
Humans
Killer Cells, Natural drug effects
Lenalidomide
Ligands
Multiple Myeloma immunology
Thalidomide pharmacology
Thalidomide therapeutic use
Killer Cells, Natural immunology
Lymphocyte Activation drug effects
Thalidomide analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 108
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 16569772
- Full Text :
- https://doi.org/10.1182/blood-2005-10-4184