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10.1038/nature19364 http://scihub22266oqcxt.onion/10.1038/nature19364 C5204372!5204372!27626381     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2016 ; 537 (7621): 539-43 Nephropedia Template TP {{tp|p=27626381|t=2016. Ionic immune suppression within the tumour microenvironment limits T cell effector function |pdf=|usr=}}{{27626381}} gab.com Text Ionic immune suppression within the tumour microenvironment limits T cell effector function JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=27626381 #FOAvip Tumours progress despite being infiltrated by tumour-specific effector T cells1. Tumours contain areas of cellular necrosis, which is associated with poor survival in a variety of cancers2. Here, we show that necrosis releases an intracellular ion, potassium, into the extracellular fluid of mouse and human tumours causing profound suppression of T cell effector function. We find that elevations in the extracellular potassium concentration [K+]e act to impair T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes, this potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A3,4. While the suppressive effect mediated by elevated [K+]e is independent of changes in plasma membrane potential (Vm), it does require an increase in intracellular potassium ([K+]i). Concordantly, ionic reprogramming of tumour-specific T cells through overexpression of the potassium channel Kv1.3 lowers [K+]i and improves effector functions in vitro and in vivo. Consequently, Kv1.3 T cell overexpression enhances tumour clearance and survival of melanoma-bearing mice. These results uncover a previously undescribed ionic checkpoint blocking T cell function within tumours and identify new strategies for cancer immunotherapy. Twit Text FOAVip Ionic immune suppression within the tumour microenvironment limits T cell effector function ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=27626381 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27626381 #FOAvip English Wikipedia <ref>{{Cite pmid|27626381}}</ref> Ionic immune suppression within the tumour microenvironment limits T cell effector function #MMPMID27626381 Eil R; Vodnala SK; Clever D; Klebanoff CA; Sukumar M; Pan JH; Palmer DC; Gros A; Yamamoto TN; Patel SJ; Guittard GC; Yu Z; Carbonaro V; Okkenhaug K; Schrump DS; Linehan WM; Roychoudhuri R; Restifo NP Nature 2016[Sep]; 537 (7621): 539-43 PMID27626381show ga Tumours progress despite being infiltrated by tumour-specific effector T cells1. Tumours contain areas of cellular necrosis, which is associated with poor survival in a variety of cancers2. Here, we show that necrosis releases an intracellular ion, potassium, into the extracellular fluid of mouse and human tumours causing profound suppression of T cell effector function. We find that elevations in the extracellular potassium concentration [K+]e act to impair T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes, this potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A3,4. While the suppressive effect mediated by elevated [K+]e is independent of changes in plasma membrane potential (Vm), it does require an increase in intracellular potassium ([K+]i). Concordantly, ionic reprogramming of tumour-specific T cells through overexpression of the potassium channel Kv1.3 lowers [K+]i and improves effector functions in vitro and in vivo. Consequently, Kv1.3 T cell overexpression enhances tumour clearance and survival of melanoma-bearing mice. These results uncover a previously undescribed ionic checkpoint blocking T cell function within tumours and identify new strategies for cancer immunotherapy. äIonic immune suppression within the tumour microenvironment limits T c(epmc).pdf DeepDyve Pubget Overpricing