| Summary: | Despite the clinical success of current immunotherapies, there remains a pressing
need to fully exploit the power of such treatments and improve their efficacy. Tumor
microenvironment (TME) crucially dictates the T-cell anti-tumor immune responses.
Yet, individual factors in the TME that drive immune suppression remains to be fully
elucidated. Dying/necrotic tumor cells release a substantial amount of intracellular
potassium ion ([K+]i), increasing extracellular potassium ion ([K+]e) to 5-10 fold. Here,
we investigated the effects of high-[K+]e on the mechanistic and functional aspects of
T-cells. We demonstrated via imaging, real-time impedance-based measurements
and molecular assays that high-[K+]e impedes T-cell motility (15% inhibition) and
possesses a chemotactic influence over T-cells. Moreover, High-[K+]e upregulates
the expression of Kv1.3 K+ channel as well as PD-1 in T-cells. Using Jurkat T-cell line
as a model, we observed that high-[K+]e reduces T-cell cytokines (IL-2 and IFN-𝛾)
production and modulates both AMPK𝛼 and ACC expression and phosphorylation,
which are prerequisite factors in cellular metabolism. Taken together, high-[K+]einduced
impairment of T-cell functions reported in the current study has implications
in T-cell anti-tumor immune responses and immunotherapies.
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