Abstract
The NF-κB pathway plays a crucial role in supporting tumor initiation, progression, and radioresistance of tumor cells. However, the role of the NF-κB pathway in radiation-induced anti-tumor host immunity remains unclear. Here we demonstrated that inhibiting the canonical NF-κB pathway dampened the therapeutic effect of ionizing radiation (IR), whereas non-canonical NF-κB deficiency promoted IR-induced anti-tumor immunity. Mechanistic studies revealed that non-canonical NF-κB 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-κB pathway resulted in decreased type I IFN expression. Administration of a specific inhibitor of the non-canonical NF-κB pathway enhanced the anti-tumor effect of IR in murine models. These findings reveal the potentially interactive roles for canonical and non-canonical NF-κB pathways in IR-induced STING-IFN production and provide an alternative strategy to improve cancer radiotherapy. It is known that the NF-κB pathway plays a crucial role in supporting tumor initiation, progression, and the radioresistance of tumor cells. Hou et al. demonstrate that the deficiency of non-canonical NF-κB, but not canonical NF-κB, promotes radiation-induced anti-tumor immunity by regulating the STING-mediated type I IFN expression.
Original language | English (US) |
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Pages (from-to) | 490-503.e4 |
Journal | Immunity |
Volume | 49 |
Issue number | 3 |
DOIs | |
State | Published - Sep 18 2018 |
Keywords
- DNA sensing
- STING
- dendritic cells
- non-canonical NF-κB
- radiotherapy
- type I IFNs
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases