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- W2296705508 abstract "Endoplasmic reticulum (ER) stress responses through the IRE-1/XBP-1 pathway are required for the function of STING (TMEM173), an ER-resident transmembrane protein critical for cytoplasmic DNA sensing, IFN production, and cancer control. Here we show that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis in normal and malignant B cells. Upon stimulation, STING was degraded less efficiently in B cells, implying that prolonged activation of STING can lead to apoptosis. Transient activation of the IRE-1/XBP-1 pathway partially protected agonist-stimulated malignant B cells from undergoing apoptosis. In Eμ-TCL1 mice with chronic lymphocytic leukemia, injection of the STING agonist 3'3'-cGAMP induced apoptosis and tumor regression. Similarly efficacious effects were elicited by 3'3'-cGAMP injection in syngeneic or immunodeficient mice grafted with multiple myeloma. Thus, in addition to their established ability to boost antitumoral immune responses, STING agonists can also directly eradicate malignant B cells. Cancer Res; 76(8); 2137-52. ©2016 AACR." @default.
- W2296705508 created "2016-06-24" @default.
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- W2296705508 date "2016-04-14" @default.
- W2296705508 modified "2023-10-14" @default.
- W2296705508 title "Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells" @default.
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- W2296705508 doi "https://doi.org/10.1158/0008-5472.can-15-1885" @default.
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