Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/182492
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dc.contributor.authorWong, Brandon Han Siangen_US
dc.contributor.authorPoh, Zhi Shengen_US
dc.contributor.authorTan, James Chia Weien_US
dc.contributor.authorAmuthavalli, Kottaiswamyen_US
dc.contributor.authorHo, Ying Swanen_US
dc.contributor.authorChen, Shuwenen_US
dc.contributor.authorMak, Shi Yaen_US
dc.contributor.authorBi, Xuezhien_US
dc.contributor.authorWebster, Richard Daviden_US
dc.contributor.authorShelat, Vishalkumar G.en_US
dc.contributor.authorChandy, Kanianthara Georgeen_US
dc.contributor.authorVerma, Navin Kumaren_US
dc.date.accessioned2025-02-04T08:22:05Z-
dc.date.available2025-02-04T08:22:05Z-
dc.date.issued2024-
dc.identifier.citationWong, B. H. S., Poh, Z. S., Tan, J. C. W., Amuthavalli, K., Ho, Y. S., Chen, S., Mak, S. Y., Bi, X., Webster, R. D., Shelat, V. G., Chandy, K. G. & Verma, N. K. (2024). High extracellular K+ skews T-cell differentiation towards tumour promoting Th2 and Treg subsets. European Journal of Immunology, e202451440-. https://dx.doi.org/10.1002/eji.202451440en_US
dc.identifier.issn0014-2980en_US
dc.identifier.urihttps://hdl.handle.net/10356/182492-
dc.description.abstractPotassium ions (K+) released from dying necrotic tumour cells accumulate in the tumour microenvironment (TME) and increase the local K+ concentration to 50 mM (high-[K+]e). Here, we demonstrate that high-[K+]e decreases expression of the T-cell receptor subunits CD3ε and CD3ζ and co-stimulatory receptor CD28 and thereby dysregulates intracellular signal transduction cascades. High-[K+]e also alters the metabolic profiles of T-cells, limiting the metabolism of glucose and glutamine, consistent with functional exhaustion. These changes skew T-cell differentiation, favouring Th2 and iTreg subsets that promote tumour growth while restricting antitumour Th1 and Th17 subsets. Similar phenotypes were noted in T-cells present within the necrosis-prone core versus the outer zones of hepatocellular carcinoma (HCC)/colorectal carcinoma (CRC) tumours as analysed by GeoMx digital spatial profiling and flow-cytometry. Our results thus expand the understanding of the contribution of high-[K+]e to the immunosuppressive milieu in the TME.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipMinistry of Health (MOH)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.description.sponsorshipNational Research Foundation (NRF)en_US
dc.language.isoenen_US
dc.relationMOE2017-T2-2-004en_US
dc.relation2020-T1-001-062en_US
dc.relationOFLCG18May-0028en_US
dc.relation.ispartofEuropean Journal of Immunologyen_US
dc.rights© 2024 The Author(s). European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the originalwork is properly cited and is not used for commercial purposes.en_US
dc.subjectMedicine, Health and Life Sciencesen_US
dc.titleHigh extracellular K+ skews T-cell differentiation towards tumour promoting Th2 and Treg subsetsen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Chemistry, Chemical Engineering and Biotechnologyen_US
dc.contributor.organizationTan Tock Seng Hospitalen_US
dc.contributor.organizationNational Skin Centre, Singaporeen_US
dc.contributor.organizationSkin Research Institute of Singaporeen_US
dc.contributor.researchNTU Institute for Health Technologiesen_US
dc.identifier.doi10.1002/eji.202451440-
dc.description.versionPublished versionen_US
dc.identifier.pmid39651799-
dc.identifier.scopus2-s2.0-85211249674-
dc.identifier.spagee202451440en_US
dc.subject.keywordsImmune suppressionen_US
dc.subject.keywordsMetabolomicsen_US
dc.description.acknowledgementThis research was supported, in part, by the Singapore Ministry of Education (MOE) under its MOE Academic Research Fund (AcRF) Tier 2 Grant (MOE2017-T2-2-004), AcRF Tier 1 Grant (2020-T1-001-062) and the National Research Foundation Singapore under its Open Fund Large Collaborative Grant (OFLCG18May-0028) and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC). Navin Kumar Verma was a recipient of these grants. Brandon Han Siang Wong and Zhi Sheng Poh are recipients of PhD fellowships from HealthTech NTU and Lee Kong Chian School of Medicine, Nanyang Technological University Singapore.en_US
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