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10.1158/1078-0432.CCR-15-3026 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-15-3026 C5010514!5010514!26979392     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 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Clin+Cancer+Res 2016 ; 22 (17): 4328-40 Nephropedia Template TP {{tp|p=26979392|t=2016. Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Anti-tumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies |pdf=|usr=}}{{26979392}} gab.com Text Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Anti-tumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26979392 #FOAvip Purpose: Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing anti-tumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically up-regulate immunosuppressive pathways, a phenomenon we term ?rebound immune suppression?, limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. Experimental Design: We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. Results: In murine models we observed marked increase in intra-tumoral IDO expression after treatment with radiotherapy, CpG or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T-cells (Tregs) in the tumor microenvironment. This triple combination induced systemic anti-tumor effects, decreasing metastases and improving survival in a CD8+ T-cell dependent manner. We evaluated this novel triple therapy in a canine clinical trial, since spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intra-tumoral immunosuppression, and induced robust systemic anti-tumor effects. Conclusion: These results suggest that IDO maintains immune suppression in the tumor after therapy and IDO blockade promotes a local anti-tumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Twit Text FOAVip Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Anti-tumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26979392 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26979392 #FOAvip English Wikipedia <ref>{{Cite pmid|26979392}}</ref> Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Anti-tumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies #MMPMID26979392 Monjazeb AM; Kent MS; Grossenbacher SK; Mall C; Zamora AE; Mirsoian A; Chen M; Kol A; Shiao SL; Reddy A; Perks JR; Culp W; Sparger EE; Canter RJ; Sckisel GD; Murphy WJ Clin Cancer Res 2016[Sep]; 22 (17): 4328-40 PMID26979392show ga Purpose: Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing anti-tumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically up-regulate immunosuppressive pathways, a phenomenon we term ?rebound immune suppression?, limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy. Experimental Design: We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial. Results: In murine models we observed marked increase in intra-tumoral IDO expression after treatment with radiotherapy, CpG or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T-cells (Tregs) in the tumor microenvironment. This triple combination induced systemic anti-tumor effects, decreasing metastases and improving survival in a CD8+ T-cell dependent manner. We evaluated this novel triple therapy in a canine clinical trial, since spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intra-tumoral immunosuppression, and induced robust systemic anti-tumor effects. Conclusion: These results suggest that IDO maintains immune suppression in the tumor after therapy and IDO blockade promotes a local anti-tumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. äBlocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts (epmc).pdf DeepDyve Pubget Overpricing