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The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFN-β pathway

Nat Immunol. 2021-03; 
Mariko Takahashi, Chan-Wang J Lio, Anaamika Campeau, Martin Steger, Ferhat Ay, Matthias Mann, David J Gonzalez, Mohit Jain, Sonia Sharma
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ORF cDNA Clones/MolecularCloud cGAS-Clover was ligated into pLV-EF1α. Human ORF clones for LMO7, MLLT6, RNF31, TRIM22, TRIM56, TRIP12, and WDR26 were obtained from GenScript Get A Quote

摘要

Evasion of host immunity is a hallmark of cancer; however, mechanisms linking oncogenic mutations and immune escape are incompletely understood. Through loss-of-function screening of 1,001 tumor suppressor genes, we identified death-associated protein kinase 3 (DAPK3) as a previously unrecognized driver of anti-tumor immunity through the stimulator of interferon genes (STING) pathway of cytosolic DNA sensing. Loss of DAPK3 expression or kinase activity impaired STING activation and interferon (IFN)-β-stimulated gene induction. DAPK3 deficiency in IFN-β-producing tumors drove rapid growth and reduced infiltration of CD103CD8α dendritic cells and cytotoxic lymphocytes, attenuating the response to cancer chemo-... More

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