Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: Therapeutic implications

David H. Chang, Nancy Liu, Virginia Klimek, Hani Hassoun, Amitabha Mazumder, Stephen D Nimer, Sundar Jagannath, Madhav V. Dhodapkar

Research output: Contribution to journalArticle

216 Citations (Scopus)

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 α-galactosylceramide (α-GalCer) in both healthy donors and patients with myeloma. NKT cells activated in the presence of LEN have greater ability to secrete interferon-γ. 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.

Original languageEnglish
Pages (from-to)618-621
Number of pages4
JournalBlood
Volume108
Issue number2
DOIs
StatePublished - Jul 15 2006
Externally publishedYes

Fingerprint

Natural Killer T-Cells
T-cells
Chemical activation
Ligands
Thalidomide
Glycolipids
Antigens
Dexamethasone
Tumors
Therapeutics
Galactosylceramides
Lymphocytes
Myelodysplastic Syndromes
Antigen Presentation
Pathogens
Interferons
lenalidomide
Neoplasms
Tissue Donors

ASJC Scopus subject areas

  • Hematology

Cite this

Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide : Therapeutic implications. / Chang, David H.; Liu, Nancy; Klimek, Virginia; Hassoun, Hani; Mazumder, Amitabha; Nimer, Stephen D; Jagannath, Sundar; Dhodapkar, Madhav V.

In: Blood, Vol. 108, No. 2, 15.07.2006, p. 618-621.

Research output: Contribution to journalArticle

Chang, DH, Liu, N, Klimek, V, Hassoun, H, Mazumder, A, Nimer, SD, Jagannath, S & Dhodapkar, MV 2006, 'Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: Therapeutic implications', Blood, vol. 108, no. 2, pp. 618-621. https://doi.org/10.1182/blood-2005-10-4184
Chang, David H. ; Liu, Nancy ; Klimek, Virginia ; Hassoun, Hani ; Mazumder, Amitabha ; Nimer, Stephen D ; Jagannath, Sundar ; Dhodapkar, Madhav V. / Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide : Therapeutic implications. In: Blood. 2006 ; Vol. 108, No. 2. pp. 618-621.
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