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 journalArticlepeer-review

219 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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