Academic Journal
High Extracellular K + Skews T‐Cell Differentiation Towards Tumour Promoting Th2 and T reg Subsets
| العنوان: | High Extracellular K + Skews T‐Cell Differentiation Towards Tumour Promoting Th2 and T reg Subsets |
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| المؤلفون: | Wong, Brandon Han Siang, Poh, Zhi Sheng, Wei, James Tan Chia, Amuthavalli, Kottaiswamy, Ho, Ying Swan, Chen, Shuwen, Mak, Shi Ya, Bi, Xuezhi, Webster, Richard D., Shelat, Vishalkumar G., Chandy, K. George, Verma, Navin Kumar |
| المصدر: | European Journal of Immunology ; ISSN 0014-2980 1521-4141 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | 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 iT reg 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/eji.202451440 |
| الاتاحة: | https://doi.org/10.1002/eji.202451440 https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.202451440 |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| رقم الانضمام: | edsbas.508EA430 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/eji.202451440 |
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