title: IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Coquet
authors.affiliation: Department of Histology and Cancer Pharmacology, Novo Nordisk A/S , Maalov, Denmark.
authors.forename: Kresten
authors.initials: K
authors.lastname: Skak
authors.affiliation: Ludwig Institute for Cancer Research, Austin Health , Melbourne, Victoria, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.affiliation: Cancer Immunology Program, Peter MacCallum Cancer Centre , East Melbourne, Victoria, Australia ; Immunology in Cancer and Infection Laboratory, Queensland Institute of Medical Research , Herston, Queensland, Australia ; School of Medicine, University of Queensland , Herston, Queensland, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
keywords: Cancer; IL-21; NKT; T helper