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Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy.
Immunity; 49(3): 490-503.e4, 2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30170810
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.

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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Idioma: Inglês Revista: Immunity Assunto da revista: Alergia e Imunologia Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Estados Unidos