| First Author | Tang CH | Year | 2016 |
| Journal | Cancer Res | Volume | 76 |
| Issue | 8 | Pages | 2137-52 |
| PubMed ID | 26951929 | Mgi Jnum | J:231775 |
| Mgi Id | MGI:5774913 | Doi | 10.1158/0008-5472.CAN-15-1885 |
| Citation | Tang CH, et al. (2016) Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells. Cancer Res 76(8):2137-52 |
| abstractText | 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 Emu-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. (c)2016 AACR. |
