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Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function

Ardena Berisha, Benjamin Jenkins, Nidhi Kedia-Mehta, Eimear K Ryan, Shauna Mayock, Odhran Ryan, Cian Davis, Helen Heneghan, Donal O’Shea, Nick Jones Orcid Logo, Andrew E Hogan

The Journal of Immunology, Volume: 215, Issue: 4, Start page: vkag073

Swansea University Authors: Benjamin Jenkins, Nick Jones Orcid Logo

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DOI (Published version): 10.1093/jimmun/vkag073

Abstract

Mucosal-associated invariant T (MAIT) cells are unconventional T cells, which upon activation can display potent cytotoxic and cytokine-producing capabilities. Together, these features make MAIT cells promising candidates for cancer immunotherapy. In this study, we show that MAIT cells can be effici...

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Published in: The Journal of Immunology
ISSN: 0022-1767 1550-6606
Published: Oxford University Press (OUP) 2026
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URI: https://cronfa.swan.ac.uk/Record/cronfa71892
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spelling 2026-06-10T11:17:05.6059241 v2 71892 2026-05-13 Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function 90f7cfd66781feba615436189178a528 Benjamin Jenkins Benjamin Jenkins true false 0fce0f7ddbdbfeb968f4e2f1e3f86744 0000-0003-4846-5117 Nick Jones Nick Jones true false 2026-05-13 MEDS Mucosal-associated invariant T (MAIT) cells are unconventional T cells, which upon activation can display potent cytotoxic and cytokine-producing capabilities. Together, these features make MAIT cells promising candidates for cancer immunotherapy. In this study, we show that MAIT cells can be efficiently amplified in vitro, and these amplified MAIT cells are armed with potent anticancer functions, including the ability to produce significant amounts of effector molecules such as IFNγ and granzyme B. Excitingly, we demonstrate that MAIT cells can be redirected to potently kill cancerous cells using a clinically relevant bispecific monoclonal antibody. Furthermore, in an attempt to metabolically condition MAIT cells to improve function, we demonstrate that MAIT cells possess the molecular machinery to transport and metabolize lactate, an abundant metabolite within the solid tumor microenvironment. Activating MAIT cells in the presence of exogenous sodium lactate remodels their cellular metabolism, with a significant increase in mitochondrial metabolism. Functionally, this supports elevated production of effector molecules (IFNγ, granzymes A and B), leading to boosted engager mediated MAIT cell cytotoxicity. These data collectively show that MAIT cells can be pharmacologically directed to target cancer cells and in vitro conditioning using sodium lactate can enhance their anticancer capabilities through reprogrammed cellular metabolism. Our findings represent a novel strategy for a potential new adoptive cancer immunotherapy. Journal Article The Journal of Immunology 215 4 vkag073 Oxford University Press (OUP) 0022-1767 1550-6606 BiTEs, immunotherapy, lactate, mucosal associated invariant T cells 30 4 2026 2026-04-30 10.1093/jimmun/vkag073 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee This study is supported by the City of Dublin Skin and Cancer Hospital Charity. A.B. is supported by Maynooth University Hume Fellowship. Financial support for the Attune NxT was provided to Maynooth University Department of Biology by Science Foundation Ireland (16/RI/3399). 2026-06-10T11:17:05.6059241 2026-05-13T14:35:54.8212434 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Ardena Berisha 1 Benjamin Jenkins 2 Nidhi Kedia-Mehta 3 Eimear K Ryan 4 Shauna Mayock 5 Odhran Ryan 6 Cian Davis 7 Helen Heneghan 8 Donal O’Shea 9 Nick Jones 0000-0003-4846-5117 10 Andrew E Hogan 11 71892__36910__7675b5b7ef294b9ea882a0e362fdb122.pdf 71892.VOR.pdf 2026-06-10T10:23:12.5727431 Output 2211076 application/pdf Version of Record true © The Author(s) 2026. Published by Oxford University Press on behalf of The American Association of Immunologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. true eng https://creativecommons.org/licenses/by/4.0/
title Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
spellingShingle Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
Benjamin Jenkins
Nick Jones
title_short Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
title_full Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
title_fullStr Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
title_full_unstemmed Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
title_sort Lactate conditioning reprograms mucosal-associated invariant T cell metabolism boosting effector function
author_id_str_mv 90f7cfd66781feba615436189178a528
0fce0f7ddbdbfeb968f4e2f1e3f86744
author_id_fullname_str_mv 90f7cfd66781feba615436189178a528_***_Benjamin Jenkins
0fce0f7ddbdbfeb968f4e2f1e3f86744_***_Nick Jones
author Benjamin Jenkins
Nick Jones
author2 Ardena Berisha
Benjamin Jenkins
Nidhi Kedia-Mehta
Eimear K Ryan
Shauna Mayock
Odhran Ryan
Cian Davis
Helen Heneghan
Donal O’Shea
Nick Jones
Andrew E Hogan
format Journal article
container_title The Journal of Immunology
container_volume 215
container_issue 4
container_start_page vkag073
publishDate 2026
institution Swansea University
issn 0022-1767
1550-6606
doi_str_mv 10.1093/jimmun/vkag073
publisher Oxford University Press (OUP)
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Mucosal-associated invariant T (MAIT) cells are unconventional T cells, which upon activation can display potent cytotoxic and cytokine-producing capabilities. Together, these features make MAIT cells promising candidates for cancer immunotherapy. In this study, we show that MAIT cells can be efficiently amplified in vitro, and these amplified MAIT cells are armed with potent anticancer functions, including the ability to produce significant amounts of effector molecules such as IFNγ and granzyme B. Excitingly, we demonstrate that MAIT cells can be redirected to potently kill cancerous cells using a clinically relevant bispecific monoclonal antibody. Furthermore, in an attempt to metabolically condition MAIT cells to improve function, we demonstrate that MAIT cells possess the molecular machinery to transport and metabolize lactate, an abundant metabolite within the solid tumor microenvironment. Activating MAIT cells in the presence of exogenous sodium lactate remodels their cellular metabolism, with a significant increase in mitochondrial metabolism. Functionally, this supports elevated production of effector molecules (IFNγ, granzymes A and B), leading to boosted engager mediated MAIT cell cytotoxicity. These data collectively show that MAIT cells can be pharmacologically directed to target cancer cells and in vitro conditioning using sodium lactate can enhance their anticancer capabilities through reprogrammed cellular metabolism. Our findings represent a novel strategy for a potential new adoptive cancer immunotherapy.
published_date 2026-04-30T06:02:24Z
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