Ionic immune suppression within the tumour microenvironment limits T cell effector function.

ABSTRACT: Tumours progress despite being infiltrated by tumour-specific effector T cells. Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers. Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K⁺]_e) impairs T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes. Potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A. Although the suppressive effect mediated by elevated [K⁺]_e is independent of changes in p

SUBMITTER: Eil R 

PROVIDER: S-EPMC5204372 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature