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Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking

CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies. He...

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Autores principales: Turaj, Anna H., Cox, Kerry L., Penfold, Christine A., French, Ruth R., Mockridge, C. Ian, Willoughby, Jane E., Tutt, Alison L., Griffiths, Jordana, Johnson, Peter W. M., Glennie, Martin J., Levy, Ronald, Cragg, Mark S., Lim, Sean H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797108/
https://www.ncbi.nlm.nih.gov/pubmed/29396470
http://dx.doi.org/10.1038/s41598-018-20656-y
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author Turaj, Anna H.
Cox, Kerry L.
Penfold, Christine A.
French, Ruth R.
Mockridge, C. Ian
Willoughby, Jane E.
Tutt, Alison L.
Griffiths, Jordana
Johnson, Peter W. M.
Glennie, Martin J.
Levy, Ronald
Cragg, Mark S.
Lim, Sean H.
author_facet Turaj, Anna H.
Cox, Kerry L.
Penfold, Christine A.
French, Ruth R.
Mockridge, C. Ian
Willoughby, Jane E.
Tutt, Alison L.
Griffiths, Jordana
Johnson, Peter W. M.
Glennie, Martin J.
Levy, Ronald
Cragg, Mark S.
Lim, Sean H.
author_sort Turaj, Anna H.
collection PubMed
description CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies. Here, we examine the expression and function of CD134 on human and mouse NK cells in B-cell lymphoma. CD134 was transiently upregulated upon activation of NK cells in both species. In contrast to CD137, induction of CD134 on human NK cells was dependent on close proximity to, or cell-to-cell contact with, monocytes or T cells. Stimulation with an agonistic anti-CD134 mAb but not CD134 ligand, increased IFNγ production and cytotoxicity of human NK cells, but this was dependent on simultaneous antibody:Fcγ receptor binding. In complementary murine studies, intravenous inoculation with BCL(1) lymphoma into immunocompetent syngeneic mice resulted in transient upregulation of CD134 on NK cells. Combination treatment with anti-CD20 and anti-CD134 mAb produced a synergistic effect with durable remissions. This therapeutic benefit was abrogated by NK cell depletion and in Fcγ chain −/− mice. Hence, anti-CD134 agonists may enhance NK-mediated anti-tumour activity in an Fcγ receptor dependent fashion.
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spelling pubmed-57971082018-02-12 Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking Turaj, Anna H. Cox, Kerry L. Penfold, Christine A. French, Ruth R. Mockridge, C. Ian Willoughby, Jane E. Tutt, Alison L. Griffiths, Jordana Johnson, Peter W. M. Glennie, Martin J. Levy, Ronald Cragg, Mark S. Lim, Sean H. Sci Rep Article CD134 (OX40) is a member of the tumour necrosis factor receptor superfamily (TNFRSF). It acts as a costimulatory receptor on T cells, but its role on NK cells is poorly understood. CD137, another TNFRSF member has been shown to enhance the anti-tumour activity of NK cells in various malignancies. Here, we examine the expression and function of CD134 on human and mouse NK cells in B-cell lymphoma. CD134 was transiently upregulated upon activation of NK cells in both species. In contrast to CD137, induction of CD134 on human NK cells was dependent on close proximity to, or cell-to-cell contact with, monocytes or T cells. Stimulation with an agonistic anti-CD134 mAb but not CD134 ligand, increased IFNγ production and cytotoxicity of human NK cells, but this was dependent on simultaneous antibody:Fcγ receptor binding. In complementary murine studies, intravenous inoculation with BCL(1) lymphoma into immunocompetent syngeneic mice resulted in transient upregulation of CD134 on NK cells. Combination treatment with anti-CD20 and anti-CD134 mAb produced a synergistic effect with durable remissions. This therapeutic benefit was abrogated by NK cell depletion and in Fcγ chain −/− mice. Hence, anti-CD134 agonists may enhance NK-mediated anti-tumour activity in an Fcγ receptor dependent fashion. Nature Publishing Group UK 2018-02-02 /pmc/articles/PMC5797108/ /pubmed/29396470 http://dx.doi.org/10.1038/s41598-018-20656-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Turaj, Anna H.
Cox, Kerry L.
Penfold, Christine A.
French, Ruth R.
Mockridge, C. Ian
Willoughby, Jane E.
Tutt, Alison L.
Griffiths, Jordana
Johnson, Peter W. M.
Glennie, Martin J.
Levy, Ronald
Cragg, Mark S.
Lim, Sean H.
Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title_full Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title_fullStr Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title_full_unstemmed Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title_short Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking
title_sort augmentation of cd134 (ox40)-dependent nk anti-tumour activity is dependent on antibody cross-linking
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797108/
https://www.ncbi.nlm.nih.gov/pubmed/29396470
http://dx.doi.org/10.1038/s41598-018-20656-y
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