@article {25843,
	title = {A bioorthogonal system reveals antitumour immune function of pyroptosis},
	journal = {Nature},
	volume = {579},
	year = {2020},
	pages = {421-426},
	abstract = {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 pyroptosis1,2,3,4,5. 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 {\textquoteleft}cleaves{\textquoteright} a designed linker that contains a silyl ether. This system enabled the controlled release of a drug from an antibody{\textendash}drug conjugate in mice. When combined with nanoparticle-mediated delivery, desilylation catalysed by Phe-BF3\&nbsp;could release a client protein{\textemdash}including an active gasdermin{\textemdash}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\&nbsp;sensitized 4T1 tumours to anti-PD1 therapy. Our bioorthogonal system based on Phe-BF3\&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.},
	url = {https://www.nature.com/articles/s41586-020-2079-1},
	author = {Qinyang Wang and Yupeng Wang and Jingjin Ding and Chunhong Wang and Xuehan Zhou and Wenqing Gao and Feng Shao and Zhibo Liu}
}
