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Title: | High extracellular K+ skews T-cell differentiation towards tumour promoting Th2 and Treg subsets | Authors: | Wong, Brandon Han Siang Poh, Zhi Sheng Tan, James Chia Wei Amuthavalli, Kottaiswamy Ho, Ying Swan Chen, Shuwen Mak, Shi Ya Bi, Xuezhi Webster, Richard David Shelat, Vishalkumar G. Chandy, Kanianthara George Verma, Navin Kumar |
Keywords: | Medicine, Health and Life Sciences | Issue Date: | 2024 | Source: | Wong, 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.202451440 | Project: | MOE2017-T2-2-004 2020-T1-001-062 OFLCG18May-0028 |
Journal: | European Journal of Immunology | Abstract: | Potassium 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. | URI: | https://hdl.handle.net/10356/182492 | ISSN: | 0014-2980 | DOI: | 10.1002/eji.202451440 | Schools: | Lee Kong Chian School of Medicine (LKCMedicine) School of Chemistry, Chemical Engineering and Biotechnology |
Organisations: | Tan Tock Seng Hospital National Skin Centre, Singapore Skin Research Institute of Singapore |
Research Centres: | NTU Institute for Health Technologies | 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. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | LKCMedicine Journal Articles |
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