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10.18632/oncotarget.24327 http://scihub22266oqcxt.onion/10.18632/oncotarget.24327 C5862579!5862579 !29568358     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=29568358 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215       Oncotarget 2018 ; 9 (17 ): 13301-13312 Nephropedia Template TP {{tp|p=29568358 |t=2018. Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy |pdf=|usr=}}{{29568358 }} gab.com Text Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=29568358 #FOAvip Research on immune checkpoint blockade therapy has made great progress in cancer immunotherapy, but the number of patients who benefit from this therapy remains limited. In this study, we examined the effects of monotherapy with systemic low-dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8(+) T cell function and accelerated regulatory T cells (Tregs) within the tumors, efficiently reduced tumor growth with more recruitment of CD8(+) T cells and a reduction of Treg. The results of resiquimod monotherapy in Colon 26, representing impaired Treg recruitment, were inferior to that in SCCVII. Combined resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it was associated with reduced tumor size, attenuation of Tregs, and an increased ratio of CD8(+) T cells/Tregs in both tumors. Systemic administration of low-dose resiquimod induced a transient and rapid activation of plasmacytoid and conventional dendritic cells, resulting in enhanced priming of T cells in regional lymph nodes. Experiments with more limited doses of resiquimod that did not yield beneficial effects after single treatment, showed additional effects to PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1 therapy was decreased. Our results suggest that systemic administration of low-dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy. Twit Text FOAVip Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=29568358 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29568358 #FOAvip English Wikipedia <ref>{{Cite pmid|29568358 }}</ref> Systemic administration of a TLR7 agonist attenuates regulatory T cells by dendritic cell modification and overcomes resistance to PD-L1 blockade therapy #MMPMID29568358 Nishii N ; Tachinami H ; Kondo Y ; Xia Y ; Kashima Y ; Ohno T ; Nagai S ; Li L ; Lau W ; Harada H ; Azuma M Oncotarget 2018[Mar]; 9 (17 ): 13301-13312 PMID29568358 show ga Research on immune checkpoint blockade therapy has made great progress in cancer immunotherapy, but the number of patients who benefit from this therapy remains limited. In this study, we examined the effects of monotherapy with systemic low-dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8(+) T cell function and accelerated regulatory T cells (Tregs) within the tumors, efficiently reduced tumor growth with more recruitment of CD8(+) T cells and a reduction of Treg. The results of resiquimod monotherapy in Colon 26, representing impaired Treg recruitment, were inferior to that in SCCVII. Combined resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it was associated with reduced tumor size, attenuation of Tregs, and an increased ratio of CD8(+) T cells/Tregs in both tumors. Systemic administration of low-dose resiquimod induced a transient and rapid activation of plasmacytoid and conventional dendritic cells, resulting in enhanced priming of T cells in regional lymph nodes. Experiments with more limited doses of resiquimod that did not yield beneficial effects after single treatment, showed additional effects to PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1 therapy was decreased. Our results suggest that systemic administration of low-dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy. ?Systemic administration of a TLR7 agonist attenuates regulatory T cell(epmc).pdf DeepDyve Pubget Overpricing