Repercussions of high extracellular K +on T-cell antitumor responses

Abstract Tumours create an immunosuppressive microenvironment that limits the antitumor function of infiltrating T-cells. Dying/necrotic tumor cells extrude intracellular potassium (K +) into local extracellular milieu, raising K +([K +] e) by 8–15 fold, which then accumulates in tumor-infiltrating Here, we determined functional impact high-[K e(50 mM) on human Using molecular assays, demonstrated prolonged exposure to ereduced CD3ɛ and CD25 (intermediate activation marker) surface expression, suggesting weakened T-cell activation. High-[K eperturbed receptor signalling downstream glycolysis pathway. metabolomics analysis, identified dysregulation pathways involving fatty acid oxidation, TCA cycle choline metabolism under e. Exposure eimpeded motility skewed polarization towards T-helper 2 (Th2) regulatory (T reg) subsets. A similar Th2 subset trend, although not significant, was seen core patient-derived biopsies (n=7) along with amassment T regcells intratumorally. Collectively, our findings substantiate effects eon functions, underlines potential use +efflux channel activators reversing dampened responses. Supported Singapore Ministry Education (MOE) its MOE Academic Research Fund (AcRF) Tier 1 Grant (2020-T1-001-062) (MOE2017-T2-2-004) grants. #LINK# #ENDLINK#