한빛사논문
- 조회524
Hyeongjwa Choi1, Juntae Kwon1, Min Soon Cho6, Yifan Sun5, Xiaofeng Zheng7, Jing Wang7, Kerrie B. Bouker8, John L. Casey3, Michael B. Atkins1,4 Jeffrey Toretsky1,2, Cecil Han1,#
1Department of Oncology, 2Departments of Pediatrics, 3Department of Microorganism and Immunology, Georgetown University School of Medicine, Washington D.C. 20007, USA; 4Division of Hematology/Oncology MedStar Georgetown University Hospital, Washington D.C. 20007, USA; 5Department of Medical and Molecular Genetics, IU School of Medicine; Indianapolis, IN 46202, USA; 6Department of Pulmonary Medicine, 7Department of Bioinformatics and Statistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 8Lombardi Comprehensive Cancer Center, Georgetown University, Washington D.C. 20007, USA.
#Correspondence
Abstract
Induction of nucleic acid sensing–mediated type I interferon (IFN) has emerged as a novel approach to activate the immune system against cancer. Here we show that the depletion of DEAD-box RNA helicase 3X (DDX3X) triggers a tumor-intrinsic type I IFN response in breast cancer cells. Depletion or inhibition of DDX3X activity led to aberrant cytoplasmic accumulation of cellular endogenous double-stranded RNAs (dsRNA), which triggered type I IFN production through the melanoma differentiation-associated gene 5 (MDA5)-mediated dsRNA-sensing pathway. Furthermore, DDX3X interacted with dsRNA-editing ADAR1 and dual depletion of DDX3X and ADAR1 synergistically activated the cytosolic dsRNA pathway in breast cancer cells. Loss of DDX3X in mouse mammary tumors enhanced antitumor activity by increasing the tumor-intrinsic type I IFN response, antigen presentation, and tumor infiltration of cytotoxic T and dendritic cells. These findings may lead to the development of a novel therapeutic approach for breast cancer by targeting DDX3X in combination with immune-checkpoint blockade.
논문정보
- Research article
- 2021년 07월 (BRIC 등록일 2021-08-12)
- 국외 연구진
- 생명과학 > 면역학
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