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Shuya Liu,1,* Saber Imani,1,* Youcai Deng,2 Janak L Pathak,3 Qinglian Wen,1 Yue Chen,4 Jingbo Wu1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Institute of Materia Medica, College of Pharmacy, Army Medical University (Third Military Medical University), Chongqing 400038, People’s Republic of China; 3Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou 510140, People’s Republic of China; 4Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingbo Wu Email wjb6147@163.comAbstract: The interferon (IFN)-mediated activation of the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling is crucial for cell sensitivity to ionizing radiation. Several preclinical studies have reported that the IFN/STAT1 pathway mediates radioresistance in the tumor microenvironment by shielding the immune responses and activating survival signaling pathways. This review focuses on the oncogenic function of the IFN/STAT1 pathway, emphasizing the major signaling pathway in radiation sensitization. Furthermore, it highlights the possibility of mediatory roles of the IFN/STAT1 pathway as a prognostic therapeutic target in the modulation of resistance to radiotherapy and chemotherapy. MicroRNA involved in the regulation of the IFN/STAT1 pathway is also discussed. A better understanding of radiation-induced IFN/STAT1 signaling will open new opportunities for the development of novel therapeutic strategies, as well as define new approaches to enhance radio-immunotherapy efficacy in the treatment of various types of cancers.Keywords: interferon-gamma signaling, signal transducer and activator of transcription 1, tumor radioresistance, IFN/STAT1, microRNA |