Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy.

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.

journal_name

Immunity

journal_title

Immunity

authors

Hou Y,Liang H,Rao E,Zheng W,Huang X,Deng L,Zhang Y,Yu X,Xu M,Mauceri H,Arina A,Weichselbaum RR,Fu YX

doi

10.1016/j.immuni.2018.07.008

subject

Has Abstract

pub_date

2018-09-18 00:00:00

pages

490-503.e4

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(18)30328-5

journal_volume

49

pub_type

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