Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells.
Cancer Res
; 76(8): 2137-52, 2016 04 15.
Article
em En
| MEDLINE
| ID: mdl-26951929
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Apoptose
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2016
Tipo de documento:
Article