| First Author | Hou Y | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 3 | Pages | 490-503.e4 |
| PubMed ID | 30170810 | Mgi Jnum | J:275850 |
| Mgi Id | MGI:6284409 | Doi | 10.1016/j.immuni.2018.07.008 |
| Citation | Hou Y, et al. (2018) Non-canonical NF-kappaB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy. Immunity 49(3):490-503.e4 |
| abstractText | The NF-kappaB pathway plays a crucial role in supporting tumor initiation, progression, and radioresistance of tumor cells. However, the role of the NF-kappaB pathway in radiation-induced anti-tumor host immunity remains unclear. Here we demonstrated that inhibiting the canonical NF-kappaB pathway dampened the therapeutic effect of ionizing radiation (IR), whereas non-canonical NF-kappaB deficiency promoted IR-induced anti-tumor immunity. Mechanistic studies revealed that non-canonical NF-kappaB signaling in dendritic cells (DCs) was activated by the STING sensor-dependent DNA-sensing pathway. By suppressing recruitment of the transcription factor RelA onto the Ifnb promoter, activation of the non-canonical NF-kappaB pathway resulted in decreased type I IFN expression. Administration of a specific inhibitor of the non-canonical NF-kappaB pathway enhanced the anti-tumor effect of IR in murine models. These findings reveal the potentially interactive roles for canonical and non-canonical NF-kappaB pathways in IR-induced STING-IFN production and provide an alternative strategy to improve cancer radiotherapy. |
