IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma

Jonathan M. Coquet, Kresten Skak, Ian D. Davis, Mark J. Smyth, Dale I. Godfrey

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12 Citations (Scopus)


Interleukin-21 (IL-21) is a common γ-chain cytokine produced by T helper and natural killer T (NKT) cells. It has been shown to regulate the response of various lymphocyte subsets including NK, NKT, T and B cells. Owing to its potent anti-tumor function in preclinical studies and its ability to induce cytotoxicity and interferon-γ (IFN-γ) production in NK and CD8 T cells, recombinant IL-21 (rIL-21) was fast-tracked into early-phase clinical trials of patients with various malignancies. In a phase 2a trial of patients with metastatic melanoma, we analyzed the frequency and function of NKT cells in patients receiving rIL-21. NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. Unlike our observations in NK and CD8 T cells, rIL-21 appeared to reduce IFN-γ and TNF production by NKT cells, whereas it enhanced IL-4 production. It also modulated the expression of cell surface markers, specifically on CD4 NKT cells. In addition, an increase in CD3+CD56+ NKT-like cells was observed over the course of rIL-21 administration. These results highlight that IL-21 is a potent regulator of NKT cell function in vivo.

Original languageEnglish
Article numbere6
Number of pages6
JournalClinical & Translational Immunology
Issue number10
Publication statusPublished - 18 Oct 2013
Externally publishedYes


  • Cancer
  • IL-21
  • NKT
  • T helper

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