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A bioorthogonal system reveals antitumour immune function of pyroptosis 期刊论文
NATURE, 2020
作者:  Kim, Sungchul;  Loeff, Luuk;  Colombo, Sabina;  Jergic, Slobodan;  Brouns, Stan J. J.;  Joo, Chirlmin
收藏  |  浏览/下载:49/0  |  提交时间:2020/07/03

Bioorthogonal chemistry capable of operating in live animals is needed to investigate biological processes such as cell death and immunity. Recent studies have identified a gasdermin family of pore-forming proteins that executes inflammasome-dependent and -independent pyroptosis(1-5). Pyroptosis is proinflammatory, but its effect on antitumour immunity is unknown. Here we establish a bioorthogonal chemical system, in which a cancer-imaging probe phenylalanine trifluoroborate (Phe-BF3) that can enter cells desilylates and '  cleaves'  a designed linker that contains a silyl ether. This system enabled the controlled release of a drug from an antibody-drug conjugate in mice. When combined with nanoparticle-mediated delivery, desilylation catalysed by Phe-BF3 could release a client protein-including an active gasdermin-from a nanoparticle conjugate, selectively into tumour cells in mice. We applied this bioorthogonal system to gasdermin, which revealed that pyroptosis of less than 15% of tumour cells was sufficient to clear the entire 4T1 mammary tumour graft. The tumour regression was absent in immune-deficient mice or upon T cell depletion, and was correlated with augmented antitumour immune responses. The injection of a reduced, ineffective dose of nanoparticle-conjugated gasdermin along with Phe-BF3 sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF3 desilylation is therefore a powerful tool for chemical biology  our application of this system suggests that pyroptosis-induced inflammation triggers robust antitumour immunity and can synergize with checkpoint blockade.


In mouse models of cancer, a biorthogonal chemical system based on desilylation catalysed by phenylalanine trifluoroborate enables the controlled release of gasdermin to induce pyroptosis selectively in tumour cells


  
Conservation, contraception and controversy: Supporting human rights to enable sustainable fisheries in Madagascar 期刊论文
GLOBAL ENVIRONMENTAL CHANGE-HUMAN AND POLICY DIMENSIONS, 2019, 59
作者:  Singleton, Rebecca L.;  Allison, Edward H.;  Gough, Charlotte;  Kamat, Vinay;  LeBillon, Philippe;  Robson, Laura;  Sumaila, U. Rashid
收藏  |  浏览/下载:13/0  |  提交时间:2020/02/17
Human rights  Small-scale fisheries  Gender equality  Sustainability  Marine conservation  PHE  Family planning  Madagascar  
Mutation of a bHLH transcription factor allowed almond domestication 期刊论文
SCIENCE, 2019, 364 (6445) : 1095-+
作者:  Sanchez-Perez, R.;  Pavan, S.;  Mazzeo, R.;  Moldovan, C.;  Aiese Cigliano, R.;  Del Cueto, J.;  Ricciardi, F.;  Lotti, C.;  Ricciardi, L.;  Dicenta, F.;  Lopez-Marques, R. L.;  Moller, B. Lindberg
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
Structural insight into precursor tRNA processing by yeast ribonuclease P 期刊论文
SCIENCE, 2018, 362 (6415) : 657-+
作者:  Lan, Pengfei;  Tan, Ming;  Zhang, Yuebin;  Niu, Shuangshuang;  Chen, Juan;  Shi, Shaohua;  Qiu, Shuwan;  Wang, Xuejuan;  Peng, Xiangda;  Cai, Gang;  Cheng, Hong;  Wu, Jian;  Li, Guohui;  Lei, Ming
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
Biomass burning influences determination based on PM2.5 chemical composition combined with fire counts at southeastern Tibetan Plateau during pre-monsoon period 期刊论文
ATMOSPHERIC RESEARCH, 2018, 206: 108-116
作者:  Zhang, Ningning;  Cao, Junji;  Wang, Qiyuan;  Huang, Rujin;  Zhu, Chongshu;  Xiao, Shun;  Wang, Linlin
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09
Biomass burning  Fire counts  Chemical composition  Aerosols  Mt. Yulong  
Increasing persistent haze in Beijing: potential impacts of weakening East Asian winter monsoons associated with northwestern Pacific sea surface temperature trends 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2018, 18 (5) : 3173-3183
作者:  Pei, Lin;  Yan, Zhongwei;  Sun, Zhaobin;  Miao, Shiguang;  Yao, Yao
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09
Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation 期刊论文
SCIENCE, 2017, 358 (6369) : 1448-1452
作者:  Aillaud, Chrystelle;  Bosc, Christophe;  Peris, Leticia;  Bosson, Anouk;  Heemeryck, Pierre;  Van Dijk, Juliette;  Le Friec, Julien;  Boulan, Benoit;  Vossier, Frederique;  Sanman, Laura E.;  Syed, Salahuddin;  Amara, Neri;  Coute, Yohann;  Lafanechere, Laurence;  Denarier, Eric;  Delphin, Christian;  Pelletier, Laurent;  Humbert, Sandrine;  Bogyo, Matthew;  Andrieux, Annie;  Rogowski, Krzysztof;  Moutin, Marie-Jo
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27