Matches in SemOpenAlex for { <https://semopenalex.org/work/W4383821992> ?p ?o ?g. }
- W4383821992 abstract "Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy." @default.
- W4383821992 created "2023-07-11" @default.
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- W4383821992 date "2023-07-10" @default.
- W4383821992 modified "2023-09-22" @default.
- W4383821992 title "ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade" @default.
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- W4383821992 doi "https://doi.org/10.1038/s41467-023-39920-5" @default.
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