2. Academic Validation
  3. Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy

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

  • Immunity. 2018 Sep 18;49(3):490-503.e4. doi: 10.1016/j.immuni.2018.07.008.
Yuzhu Hou 1,  Hua Liang 1,  Enyu Rao 2,  Wenxin Zheng 1,  Xiaona Huang 1,  Liufu Deng 3,  Yuan Zhang 1,  Xinshuang Yu 4,  Meng Xu 1,  Helena Mauceri 1,  Ainhoa Arina 1,  Ralph R Weichselbaum 5,  Yang-Xin Fu 6
Affiliations

Affiliations

  • 1 Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.
  • 2 Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA; Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA; Shanghai Institute of Immunology; Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, China.
  • 4 Department of Radiation Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
  • 5 Ludwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: rrw@radonc.uchicago.edu.
  • 6 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9072, USA. Electronic address: yang-xin.fu@utsouthwestern.edu.
PMID: 30170810 DOI: 10.1016/j.immuni.2018.07.008
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.

Keywords

DNA sensing; STING; dendritic cells; non-canonical NF-κB; radiotherapy; type I IFNs.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P3229
    99.82%, NF-κB2抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z