Matches in SemOpenAlex for { <https://semopenalex.org/work/W2776126183> ?p ?o ?g. }
- W2776126183 endingPage "786" @default.
- W2776126183 startingPage "777" @default.
- W2776126183 abstract "Immunotherapy has increasingly become a staple in cancer treatment. However, substantial limitations in the durability of response highlight the need for more rational therapeutic combinations. The aim of this study is to investigate how to make tumor cells more sensitive to T-cell-based cancer immunotherapy.Two pairs of melanoma patient-derived tumor cell lines and their autologous tumor-infiltrating lymphocytes were utilized in a high-throughput screen of 850 compounds to identify bioactive agents that could be used in combinatorial strategies to improve T-cell-mediated killing of tumor cells. RNAi, overexpression, and gene expression analyses were utilized to identify the mechanism underlying the effect of Topoisomerase I (Top1) inhibitors on T-cell-mediated killing. Using a syngeneic mouse model (n = 5 per group), the antitumor efficacy of the combination of a clinically relevant Top1 inhibitor, liposomal irinotecan (MM-398), with immune checkpoint inhibitors was also assessed. All statistical tests were two-sided.We found that Top1 inhibitors increased the sensitivity of patient-derived melanoma cell lines (n = 7) to T-cell-mediated cytotoxicity (P < .001, Dunnett's test). This enhancement is mediated by TP53INP1, whose overexpression increased the susceptibility of melanoma cell lines to T-cell cytotoxicity (2549 cell line: P = .009, unpaired t test), whereas its knockdown impeded T-cell killing of Top1 inhibitor-treated melanoma cells (2549 cell line: P < .001, unpaired t test). In vivo, greater tumor control was achieved with MM-398 in combination with α-PD-L1 or α-PD1 (P < .001, Tukey's test). Prolonged survival was also observed in tumor-bearing mice treated with MM-398 in combination with α-PD-L1 (P = .002, log-rank test) or α-PD1 (P = .008, log-rank test).We demonstrated that Top1 inhibitors can improve the antitumor efficacy of cancer immunotherapy, thus providing the basis for developing novel strategies using Top1 inhibitors to augment the efficacy of immunotherapy." @default.
- W2776126183 created "2018-01-05" @default.
- W2776126183 creator A5000507404 @default.
- W2776126183 creator A5002244239 @default.
- W2776126183 creator A5009215882 @default.
- W2776126183 creator A5009442045 @default.
- W2776126183 creator A5012044195 @default.
- W2776126183 creator A5014508276 @default.
- W2776126183 creator A5024061893 @default.
- W2776126183 creator A5027858037 @default.
- W2776126183 creator A5027861576 @default.
- W2776126183 creator A5029017725 @default.
- W2776126183 creator A5033798832 @default.
- W2776126183 creator A5035961942 @default.
- W2776126183 creator A5043392987 @default.
- W2776126183 creator A5045360918 @default.
- W2776126183 creator A5050132330 @default.
- W2776126183 creator A5051328429 @default.
- W2776126183 creator A5052134746 @default.
- W2776126183 creator A5053204257 @default.
- W2776126183 creator A5061655507 @default.
- W2776126183 creator A5062055196 @default.
- W2776126183 creator A5062622724 @default.
- W2776126183 creator A5065349307 @default.
- W2776126183 creator A5066028652 @default.
- W2776126183 creator A5066354365 @default.
- W2776126183 creator A5071360122 @default.
- W2776126183 creator A5072305917 @default.
- W2776126183 creator A5089088185 @default.
- W2776126183 creator A5089324640 @default.
- W2776126183 date "2017-12-18" @default.
- W2776126183 modified "2023-10-17" @default.
- W2776126183 title "The Effect of Topoisomerase I Inhibitors on the Efficacy of T-Cell-Based Cancer Immunotherapy" @default.
- W2776126183 cites W115026875 @default.
- W2776126183 cites W1498931318 @default.
- W2776126183 cites W1809627231 @default.
- W2776126183 cites W1950829641 @default.
- W2776126183 cites W1979490110 @default.
- W2776126183 cites W1980881639 @default.
- W2776126183 cites W1994993231 @default.
- W2776126183 cites W1995068068 @default.
- W2776126183 cites W2002010679 @default.
- W2776126183 cites W2008100329 @default.
- W2776126183 cites W2010121426 @default.
- W2776126183 cites W2026263500 @default.
- W2776126183 cites W2028433016 @default.
- W2776126183 cites W2047265596 @default.
- W2776126183 cites W2069452349 @default.
- W2776126183 cites W2074801788 @default.
- W2776126183 cites W2084831115 @default.
- W2776126183 cites W2096439168 @default.
- W2776126183 cites W2096522498 @default.
- W2776126183 cites W2097995306 @default.
- W2776126183 cites W2098414192 @default.
- W2776126183 cites W2107484016 @default.
- W2776126183 cites W2118863472 @default.
- W2776126183 cites W2123363005 @default.
- W2776126183 cites W2129769331 @default.
- W2776126183 cites W2156353875 @default.
- W2776126183 cites W2160834915 @default.
- W2776126183 cites W2166885734 @default.
- W2776126183 cites W2171120503 @default.
- W2776126183 cites W2173135538 @default.
- W2776126183 cites W2201379305 @default.
- W2776126183 cites W2222086386 @default.
- W2776126183 cites W2465860350 @default.
- W2776126183 cites W2560367415 @default.
- W2776126183 cites W2572174216 @default.
- W2776126183 doi "https://doi.org/10.1093/jnci/djx257" @default.
- W2776126183 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6037061" @default.
- W2776126183 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29267866" @default.
- W2776126183 hasPublicationYear "2017" @default.
- W2776126183 type Work @default.
- W2776126183 sameAs 2776126183 @default.
- W2776126183 citedByCount "51" @default.
- W2776126183 countsByYear W27761261832018 @default.
- W2776126183 countsByYear W27761261832019 @default.
- W2776126183 countsByYear W27761261832020 @default.
- W2776126183 countsByYear W27761261832021 @default.
- W2776126183 countsByYear W27761261832022 @default.
- W2776126183 countsByYear W27761261832023 @default.
- W2776126183 crossrefType "journal-article" @default.
- W2776126183 hasAuthorship W2776126183A5000507404 @default.
- W2776126183 hasAuthorship W2776126183A5002244239 @default.
- W2776126183 hasAuthorship W2776126183A5009215882 @default.
- W2776126183 hasAuthorship W2776126183A5009442045 @default.
- W2776126183 hasAuthorship W2776126183A5012044195 @default.
- W2776126183 hasAuthorship W2776126183A5014508276 @default.
- W2776126183 hasAuthorship W2776126183A5024061893 @default.
- W2776126183 hasAuthorship W2776126183A5027858037 @default.
- W2776126183 hasAuthorship W2776126183A5027861576 @default.
- W2776126183 hasAuthorship W2776126183A5029017725 @default.
- W2776126183 hasAuthorship W2776126183A5033798832 @default.
- W2776126183 hasAuthorship W2776126183A5035961942 @default.
- W2776126183 hasAuthorship W2776126183A5043392987 @default.
- W2776126183 hasAuthorship W2776126183A5045360918 @default.
- W2776126183 hasAuthorship W2776126183A5050132330 @default.
- W2776126183 hasAuthorship W2776126183A5051328429 @default.