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10.1038/s41467-017-00728-9 http://scihub22266oqcxt.onion/10.1038/s41467-017-00728-9 C5605577!5605577 !28928458     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28928458 &cmd=llinks): Failed to open stream: HTTP request failed! 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Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer |pdf=|usr=}}{{28928458 }} gab.com Text Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28928458 #FOAvip The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that ?-4-1BB and ?-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. This effect is dependent upon increased downstream p38/JNK pathway activation. Taken together, our data suggest that although Ras/MAPK pathway inhibition can increase tumor immunogenicity, the negative impact on T-cell activity is functionally important. This undesirable impact is effectively prevented by combination with T-cell immune agonist immunotherapies resulting in superior therapeutic efficacy.MEK inhibition in breast cancer is associated with increased tumour infiltrating lymphocytes (TILs), however, MAPK activity is required for T cells function. Here the authors show that TILs activity following MEK inhibition can be enhanced by agonist immunotherapy resulting in synergic therapeutic effects. Twit Text FOAVip Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28928458 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28928458 #FOAvip English Wikipedia <ref>{{Cite pmid|28928458 }}</ref> Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer #MMPMID28928458 Dushyanthen S ; Teo ZL ; Caramia F ; Savas P ; Mintoff CP ; Virassamy B ; Henderson MA ; Luen SJ ; Mansour M ; Kershaw MH ; Trapani JA ; Neeson PJ ; Salgado R ; McArthur GA ; Balko JM ; Beavis PA ; Darcy PK ; Loi S Nat Commun 2017[Sep]; 8 (1 ): 606 PMID28928458 show ga The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that ?-4-1BB and ?-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. This effect is dependent upon increased downstream p38/JNK pathway activation. Taken together, our data suggest that although Ras/MAPK pathway inhibition can increase tumor immunogenicity, the negative impact on T-cell activity is functionally important. This undesirable impact is effectively prevented by combination with T-cell immune agonist immunotherapies resulting in superior therapeutic efficacy.MEK inhibition in breast cancer is associated with increased tumour infiltrating lymphocytes (TILs), however, MAPK activity is required for T cells function. Here the authors show that TILs activity following MEK inhibition can be enhanced by agonist immunotherapy resulting in synergic therapeutic effects. |*Immunotherapy [MESH] |4-1BB Ligand/*agonists [MESH] |Animals [MESH] |Breast Neoplasms/immunology [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/*drug effects [MESH] |Female [MESH] |Humans [MESH] |Lymphocytes, Tumor-Infiltrating/*drug effects/immunology [MESH] |MAP Kinase Kinase 1/antagonists & inhibitors [MESH] |MAP Kinase Kinase 2/antagonists & inhibitors [MESH] |MAP Kinase Signaling System/drug effects/immunology [MESH] |Mammary Neoplasms, Animal/*immunology [MESH] |Mice [MESH] |OX40 Ligand/*agonists [MESH] |Protein Kinase Inhibitors/*pharmacology [MESH] |Pyridones/*pharmacology [MESH] |Pyrimidinones/*pharmacology [MESH] |T-Lymphocyte Subsets/*drug effects [MESH] |T-Lymphocytes/drug effects [MESH]Agonist immunotherapy restores T cell function following MEK inhibitio(epmc).pdf DeepDyve Pubget Overpricing