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|Title:||IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma.||Austin Authors:||Coquet, Jonathan M;Skak, Kresten;Davis, Ian D;Smyth, Mark J;Godfrey, Dale I||Affiliation:||Ludwig Institute for Cancer Research, Austin Health , Melbourne, Victoria, Australia
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
Department of Microbiology and Immunology, University of Melbourne , Parkville, Victoria, Australia
Department of Histology and Cancer Pharmacology, Novo Nordisk A/S , Maalov, Denmark.
|Issue Date:||18-Oct-2013||Publication information:||Clinical & Translational Immunology 2013; 2(10): e6||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.||Gov't Doc #:||25505948||URI:||http://ahro.austin.org.au/austinjspui/handle/1/12535||DOI:||10.1038/cti.2013.7||Journal:||Clinical & translational immunology||URL:||https://pubmed.ncbi.nlm.nih.gov/25505948||Type:||Journal Article||Subjects:||Cancer
|Appears in Collections:||Journal articles|
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