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

Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody crosslinking
Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody crosslinking
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 BCL1 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.
2045-2322
1-11
Turaj, Anna H.
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Cox, Kerry L.
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Penfold, Christine A.
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French, Ruth R.
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Mockridge, C. Ian
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Willoughby, Jane E.
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Tutt, Alison L.
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Griffiths, Jordana
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Johnson, Peter W.M.
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Glennie, Martin J.
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Levy, Ronald
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Cragg, Mark S.
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Lim, Sean H.
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Lim, Sean H.
1afe5aa1-61a4-4a7b-927f-5e671f885196
Turaj, Anna H.
fbbc48ea-28cf-4db7-ae4a-c16ce7b3857a
Cox, Kerry L.
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Penfold, Christine A.
400d743e-a639-45ea-a027-5b778800f6d3
French, Ruth R.
a95ea7a1-7aeb-4c20-998e-fde663613fd1
Mockridge, C. Ian
ced95edf-26ca-42e5-b1f2-946bb6c813f6
Willoughby, Jane E.
aa6969bd-3830-4e1b-83ac-6369b5711e1f
Tutt, Alison L.
46ce577b-aea1-412d-84ea-fc4dab794469
Griffiths, Jordana
dfd2130a-fd5b-4c17-bb7b-321dd5d24ecb
Johnson, Peter W.M.
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Glennie, Martin J.
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Levy, Ronald
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Cragg, Mark S.
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Lim, Sean H.
1afe5aa1-61a4-4a7b-927f-5e671f885196
Lim, Sean H.
1afe5aa1-61a4-4a7b-927f-5e671f885196

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. and Lim, Sean H. (2018) Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody crosslinking. Scientific Reports, 8 (1), 1-11. (doi:10.1038/s41598-018-20656-y).

Record type: Article

Abstract

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 BCL1 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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More information

Accepted/In Press date: 22 January 2018
e-pub ahead of print date: 2 February 2018
Published date: 1 December 2018

Identifiers

Local EPrints ID: 418129
URI: https://eprints.soton.ac.uk/id/eprint/418129
ISSN: 2045-2322
PURE UUID: 7bc38f11-d62b-42b3-80e2-5076e8fba37e
ORCID for Peter W.M. Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Mark S. Cragg: ORCID iD orcid.org/0000-0003-2077-089X

Catalogue record

Date deposited: 22 Feb 2018 17:30
Last modified: 14 Mar 2019 01:49

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