FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2737010615> ?p ?o ?g. }

• W2737010615 abstract "T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME).In mice, the effects of MEK inhibition, via selumetinib, and anti-CTLA-4 on immune responses to keyhole limpet haemocyanin (KLH) immunization were monitored using ex vivo functional assays with splenocytes. In a KRAS-mutant CT26 mouse colorectal cancer model, the impact on the tumor microenvironment (TME) and the spleen were evaluated by flow cytometry. The TME was further examined by gene expression and immunohistochemical analyses. The combination and sequencing of selumetinib and anti-CTLA-4 were also evaluated in efficacy studies using the CT26 mouse syngeneic model.Anti-CTLA-4 enhanced the generation of KLH specific immunity following KLH immunization in vivo; selumetinib was found to reduce, but did not prevent, this enhancement of immune response by anti-CTLA-4 in vivo. In the CT26 mouse model, anti-CTLA-4 treatment led to higher expression levels of the immunosuppressive mediators, Cox-2 and Arg1 in the TME. Combination of anti-CTLA-4 with selumetinib negated this up-regulation of Cox-2 and Arg1, reduced the frequency of CD11+ Ly6G+ myeloid cells, and led to the accumulation of differentiating monocytes at the Ly6C+ MHC+ intermediate state in the tumor. We also report that MEK inhibition had limited impact on anti-CTLA-4-mediated increases in T-cell infiltration and T-cell activation in CT26 tumors. Finally, we show that pre-treatment, but not concurrent treatment, with selumetinib enhanced the anti-tumor activity of anti-CTLA-4 in the CT26 model.These data provide evidence that MEK inhibition can lead to changes in myeloid cells and immunosuppressive factors in the tumor, thus potentially conditioning the TME to facilitate improved response to anti-CTLA-4 treatment. In summary, the use of MEK inhibitors to alter the TME as an approach to enhance the activities of immune checkpoint inhibitors warrants further investigation in clinical trials." @default.
• W2737010615 created "2017-07-31" @default.
• W2737010615 creator A5003340825 @default.
• W2737010615 creator A5008233699 @default.
• W2737010615 creator A5012838760 @default.
• W2737010615 creator A5014348413 @default.
• W2737010615 creator A5027618078 @default.
• W2737010615 creator A5031881855 @default.
• W2737010615 creator A5032425544 @default.
• W2737010615 creator A5034405695 @default.
• W2737010615 creator A5037419868 @default.
• W2737010615 creator A5038010720 @default.
• W2737010615 creator A5041444624 @default.
• W2737010615 creator A5044215747 @default.
• W2737010615 creator A5055595135 @default.
• W2737010615 creator A5070997628 @default.
• W2737010615 creator A5073399228 @default.
• W2737010615 creator A5079557793 @default.
• W2737010615 date "2017-08-15" @default.
• W2737010615 modified "2023-10-16" @default.
• W2737010615 title "The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment" @default.
• W2737010615 cites W1524005671 @default.
• W2737010615 cites W1848470479 @default.
• W2737010615 cites W1921451985 @default.
• W2737010615 cites W1925817305 @default.
• W2737010615 cites W1933761723 @default.
• W2737010615 cites W1949265142 @default.
• W2737010615 cites W1972755885 @default.
• W2737010615 cites W1977315768 @default.
• W2737010615 cites W2015069573 @default.
• W2737010615 cites W2032879966 @default.
• W2737010615 cites W2038914273 @default.
• W2737010615 cites W2058142370 @default.
• W2737010615 cites W2060672294 @default.
• W2737010615 cites W2077508806 @default.
• W2737010615 cites W2078490888 @default.
• W2737010615 cites W2094481139 @default.
• W2737010615 cites W2099044540 @default.
• W2737010615 cites W2101581360 @default.
• W2737010615 cites W2104925898 @default.
• W2737010615 cites W2114671410 @default.
• W2737010615 cites W2116376943 @default.
• W2737010615 cites W2118106910 @default.
• W2737010615 cites W2120407692 @default.
• W2737010615 cites W2121294918 @default.
• W2737010615 cites W2140683554 @default.
• W2737010615 cites W2149639441 @default.
• W2737010615 cites W2155364136 @default.
• W2737010615 cites W2162147795 @default.
• W2737010615 cites W2172917669 @default.
• W2737010615 cites W2257916459 @default.
• W2737010615 cites W2289851792 @default.
• W2737010615 cites W2513415897 @default.
• W2737010615 cites W2526479644 @default.
• W2737010615 cites W2529896336 @default.
• W2737010615 cites W2541831810 @default.
• W2737010615 cites W2613467753 @default.
• W2737010615 cites W2890038459 @default.
• W2737010615 doi "https://doi.org/10.1186/s40425-017-0268-8" @default.
• W2737010615 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5557252" @default.
• W2737010615 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28807001" @default.
• W2737010615 hasPublicationYear "2017" @default.
• W2737010615 type Work @default.
• W2737010615 sameAs 2737010615 @default.
• W2737010615 citedByCount "55" @default.
• W2737010615 countsByYear W27370106152017 @default.
• W2737010615 countsByYear W27370106152018 @default.
• W2737010615 countsByYear W27370106152019 @default.
• W2737010615 countsByYear W27370106152020 @default.
• W2737010615 countsByYear W27370106152021 @default.
• W2737010615 countsByYear W27370106152022 @default.
• W2737010615 countsByYear W27370106152023 @default.
• W2737010615 crossrefType "journal-article" @default.
• W2737010615 hasAuthorship W2737010615A5003340825 @default.
• W2737010615 hasAuthorship W2737010615A5008233699 @default.
• W2737010615 hasAuthorship W2737010615A5012838760 @default.
• W2737010615 hasAuthorship W2737010615A5014348413 @default.
• W2737010615 hasAuthorship W2737010615A5027618078 @default.
• W2737010615 hasAuthorship W2737010615A5031881855 @default.
• W2737010615 hasAuthorship W2737010615A5032425544 @default.
• W2737010615 hasAuthorship W2737010615A5034405695 @default.
• W2737010615 hasAuthorship W2737010615A5037419868 @default.
• W2737010615 hasAuthorship W2737010615A5038010720 @default.
• W2737010615 hasAuthorship W2737010615A5041444624 @default.
• W2737010615 hasAuthorship W2737010615A5044215747 @default.
• W2737010615 hasAuthorship W2737010615A5055595135 @default.
• W2737010615 hasAuthorship W2737010615A5070997628 @default.
• W2737010615 hasAuthorship W2737010615A5073399228 @default.
• W2737010615 hasAuthorship W2737010615A5079557793 @default.
• W2737010615 hasBestOaLocation W27370106151 @default.
• W2737010615 hasConcept C154317977 @default.
• W2737010615 hasConcept C202751555 @default.
• W2737010615 hasConcept C203014093 @default.
• W2737010615 hasConcept C21705690 @default.
• W2737010615 hasConcept C2776087337 @default.
• W2737010615 hasConcept C2776090121 @default.
• W2737010615 hasConcept C2776107976 @default.
• W2737010615 hasConcept C2777701055 @default.
• W2737010615 hasConcept C2780851360 @default.
• W2737010615 hasConcept C2781249067 @default.

• next