<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Qinyang Wang</style></author><author><style face="normal" font="default" size="100%">Yupeng Wang</style></author><author><style face="normal" font="default" size="100%">Jingjin Ding</style></author><author><style face="normal" font="default" size="100%">Chunhong Wang</style></author><author><style face="normal" font="default" size="100%">Xuehan Zhou</style></author><author><style face="normal" font="default" size="100%">Wenqing Gao</style></author><author><style face="normal" font="default" size="100%">Feng Shao</style></author><author><style face="normal" font="default" size="100%">Zhibo Liu</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A bioorthogonal system reveals antitumour immune function of pyroptosis</style></title><secondary-title><style face="normal" font="default" size="100%">Nature</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2020</style></year></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.nature.com/articles/s41586-020-2079-1</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">579</style></volume><pages><style face="normal" font="default" size="100%">421-426</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">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&lt;a id=&quot;ref-link-section-d38956e507&quot; href=&quot;https://www.nature.com/articles/s41586-020-2079-1#ref-CR1&quot; title=&quot;Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526, 666–671 (2015).&quot; data-track=&quot;click&quot; data-track-action=&quot;reference anchor&quot; data-track-label=&quot;link&quot; data-test=&quot;citation-ref&quot;&gt;1&lt;/a&gt;,&lt;a id=&quot;ref-link-section-d38956e507_1&quot; href=&quot;https://www.nature.com/articles/s41586-020-2079-1#ref-CR2&quot; title=&quot;Shi, J. et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526, 660–665 (2015).&quot; data-track=&quot;click&quot; data-track-action=&quot;reference anchor&quot; data-track-label=&quot;link&quot; data-test=&quot;citation-ref&quot;&gt;2&lt;/a&gt;,&lt;a id=&quot;ref-link-section-d38956e507_2&quot; href=&quot;https://www.nature.com/articles/s41586-020-2079-1#ref-CR3&quot; title=&quot; gasdermin-mediated programmed necrotic cell death. Trends Biochem. Sci. 42, 245–254 (2017).&quot; data-track=&quot;click&quot; data-track-action=&quot;reference anchor&quot; data-track-label=&quot;link&quot; data-test=&quot;citation-ref&quot;&gt;3&lt;/a&gt;,&lt;a id=&quot;ref-link-section-d38956e507_3&quot; href=&quot;https://www.nature.com/articles/s41586-020-2079-1#ref-CR4&quot; title=&quot;Wang, Y. et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547, 99–103 (2017).&quot; data-track=&quot;click&quot; data-track-action=&quot;reference anchor&quot; data-track-label=&quot;link&quot; data-test=&quot;citation-ref&quot;&gt;4&lt;/a&gt;,&lt;a id=&quot;ref-link-section-d38956e510&quot; href=&quot;https://www.nature.com/articles/s41586-020-2079-1#ref-CR5&quot; title=&quot;//doi.org/10.1038/s41577-019-0228-2

 (2019).&quot; data-track=&quot;click&quot; data-track-action=&quot;reference anchor&quot; data-track-label=&quot;link&quot; data-test=&quot;citation-ref&quot;&gt;5&lt;/a&gt;. 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&amp;nbsp;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&amp;nbsp;sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF3&amp;nbsp;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.</style></abstract></record></records></xml>