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10.1038/ncomms15618 http://scihub22266oqcxt.onion/10.1038/ncomms15618 C5472757!5472757 !28598415     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28598415 &cmd=llinks): Failed to open stream: HTTP request failed! 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DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity |pdf=|usr=}}{{28598415 }} gab.com Text DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28598415 #FOAvip Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-? by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-? production, resulting in recruitment and activation of Batf3-dependent dendritic cells. This effect is essential for priming of CD8(+) T cells that mediate systemic tumour rejection (abscopal effect) in the context of immune checkpoint blockade. Thus, Trex1 is an upstream regulator of radiation-driven anti-tumour immunity. Trex1 induction may guide the selection of radiation dose and fractionation in patients treated with immunotherapy. Twit Text FOAVip DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=28598415 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28598415 #FOAvip English Wikipedia <ref>{{Cite pmid|28598415 }}</ref> DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity #MMPMID28598415 Vanpouille-Box C ; Alard A ; Aryankalayil MJ ; Sarfraz Y ; Diamond JM ; Schneider RJ ; Inghirami G ; Coleman CN ; Formenti SC ; Demaria S Nat Commun 2017[Jun]; 8 (ä): 15618 PMID28598415 show ga Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-? by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-? production, resulting in recruitment and activation of Batf3-dependent dendritic cells. This effect is essential for priming of CD8(+) T cells that mediate systemic tumour rejection (abscopal effect) in the context of immune checkpoint blockade. Thus, Trex1 is an upstream regulator of radiation-driven anti-tumour immunity. Trex1 induction may guide the selection of radiation dose and fractionation in patients treated with immunotherapy. |Animals [MESH] |Basic-Leucine Zipper Transcription Factors/immunology [MESH] |CD8-Positive T-Lymphocytes/*immunology/radiation effects [MESH] |CTLA-4 Antigen/immunology [MESH] |Cell Line, Tumor [MESH] |Dendritic Cells/*immunology/radiation effects [MESH] |Exodeoxyribonucleases/*metabolism/*radiation effects [MESH] |Female [MESH] |Gene Expression Regulation/genetics/immunology [MESH] |HEK293 Cells [MESH] |Humans [MESH] |Immunotherapy/methods [MESH] |Interferon-beta/metabolism/radiation effects [MESH] |Mammary Neoplasms, Animal/*genetics/pathology [MESH] |Membrane Proteins/metabolism [MESH] |Mice [MESH] |Mice, Inbred BALB C [MESH] |Mice, Inbred C57BL [MESH] |Mice, Inbred NOD [MESH] |Mice, Knockout [MESH] |Mice, SCID [MESH] |Neoplasms/*immunology/*radiotherapy [MESH] |Nucleotidyltransferases/metabolism [MESH] |Phosphoproteins/*metabolism/*radiation effects [MESH] |Receptor, Interferon alpha-beta/genetics/immunology [MESH]DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogeni(epmc).pdf DeepDyve Pubget Overpricing