Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/182492
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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