Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1073/pnas.1512832112 http://scihub22266oqcxt.onion/10.1073/pnas.1512832112 C4687570!4687570 !26607445     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26607445 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Proc+Natl+Acad+Sci+U+S+A 2015 ; 112 (50 ): 15408-13 Nephropedia Template TP {{tp|p=26607445 |t=2015. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity |pdf=|usr=}}{{26607445 }} gab.com Text STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=26607445 #FOAvip Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma. Twit Text FOAVip STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=26607445 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26607445 #FOAvip English Wikipedia <ref>{{Cite pmid|26607445 }}</ref> STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity #MMPMID26607445 Demaria O ; De Gassart A ; Coso S ; Gestermann N ; Di Domizio J ; Flatz L ; Gaide O ; Michielin O ; Hwu P ; Petrova TV ; Martinon F ; Modlin RL ; Speiser DE ; Gilliet M Proc Natl Acad Sci U S A 2015[Dec]; 112 (50 ): 15408-13 PMID26607445 show ga Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma. |*Immunity [MESH] |Animals [MESH] |Antigens, Neoplasm/immunology [MESH] |CD8-Positive T-Lymphocytes/immunology [MESH] |CTLA-4 Antigen/immunology [MESH] |Cell Proliferation/drug effects [MESH] |Dendritic Cells/drug effects/immunology [MESH] |Disease Models, Animal [MESH] |Dose-Response Relationship, Immunologic [MESH] |Endothelial Cells/drug effects/*metabolism [MESH] |Injections, Intralesional [MESH] |Interferon Type I/metabolism [MESH] |Lymphocytes, Tumor-Infiltrating/drug effects/immunology [MESH] |Melanoma, Experimental/immunology/pathology [MESH] |Melanoma/immunology/pathology [MESH] |Membrane Proteins/*metabolism [MESH] |Mice, Inbred C57BL [MESH] |Neoplasms/*immunology/pathology/*therapy [MESH] |Nucleotides, Cyclic/administration & dosage/pharmacology [MESH] |Receptor, Interferon alpha-beta/metabolism [MESH]STING activation of tumor endothelial cells initiates spontaneous and (epmc).pdf DeepDyve Pubget Overpricing