High Extracellular K<sup>+</sup> Skews T-Cell Differentiation Towards Tumour Promoting Th2 and T<sub>reg</sub> Subsets.
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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 wer
SUBMITTER: Wong BHS
PROVIDER: S-EPMC11830381 | biostudies-literature | 2025 Feb
REPOSITORIES: biostudies-literature
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