Oncolytic virus treatment differentially affects the CD56 dim and CD56 bright NK cell subsets in vivo and regulates a spectrum of human NK cell activity.

Autor: Wantoch M; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Wilson EB; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Droop AP; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Phillips SL; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Coffey M; Oncolytics Biotech Inc, Calgary, Alberta, Canada., El-Sherbiny YM; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Holmes TD; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Melcher AA; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Wetherill LF; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK., Cook GP; Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, UK.
Jazyk: angličtina
Zdroj: Immunology [Immunology] 2022 May; Vol. 166 (1), pp. 104-120. Date of Electronic Publication: 2022 Mar 09.
DOI: 10.1111/imm.13453
Abstrakt: Natural killer (NK) cells protect against intracellular infection and cancer. These properties are exploited in oncolytic virus (OV) therapy, where antiviral responses enhance anti-tumour immunity. We have analysed the mechanism by which reovirus, an oncolytic dsRNA virus, modulates human NK cell activity. Reovirus activates NK cells in a type I interferon (IFN-I) dependent manner, inducing STAT1 and STAT4 signalling in both CD56 dim and CD56 bright NK cell subsets. Gene expression profiling revealed the dominance of IFN-I responses and identified induction of genes associated with NK cell cytotoxicity and cell cycle progression, with distinct responses in the CD56 dim and CD56 bright subsets. However, reovirus treatment inhibited IL-15 induced NK cell proliferation in an IFN-I dependent manner and was associated with reduced AKT signalling. In vivo, human CD56 dim and CD56 bright NK cells responded with similar kinetics to reovirus treatment, but CD56 bright NK cells were transiently lost from the peripheral circulation at the peak of the IFN-I response, suggestive of their redistribution to secondary lymphoid tissue. Coupled with the direct, OV-mediated killing of tumour cells, the activation of both CD56 dim and CD56 bright NK cells by antiviral pathways induces a spectrum of activity that includes the NK cell-mediated killing of tumour cells and modulation of adaptive responses via the trafficking of IFN-γ expressing CD56 bright NK cells to lymph nodes.
(© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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