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- Title
Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways.
- Authors
Du, Junyan; Kageyama, Shun-Ichiro; Yamashita, Riu; Tanaka, Kosuke; Okumura, Masayuki; Motegi, Atsushi; Hojo, Hidehiro; Nakamura, Masaki; Hirata, Hidenari; Sunakawa, Hironori; Kotani, Daisuke; Yano, Tomonori; Kojima, Takashi; Hamaya, Yamato; Kojima, Motohiro; Nakamura, Yuka; Suzuki, Ayako; Suzuki, Yutaka; Tsuchihara, Katsuya; Akimoto, Tetsuo
- Abstract
Radiotherapy (RT) plus immunotherapy is a promising modality; however, the therapeutic effects are insufficient, and the molecular mechanism requires clarification to further develop combination therapies. Here, we found that the RNA virus sensor pathway dominantly regulates the cellular immune response in NSCLC and ESCC cell lines. Notably, transposable elements (TEs), especially long terminal repeats (LTRs), functioned as key ligands for the RNA virus sensor RIG-I, and the mTOR–LTR–RIG-I axis induced the cellular immune response and dendritic cell and macrophage infiltration after irradiation. Moreover, RIG-I-dependent immune activation was observed in ESCC patient tissue. scRNA sequencing and spatial transcriptome analysis revealed that radiotherapy induced the expression of LTRs, and the RNA virus sensor pathway in immune and cancer cells; this pathway was also found to mediate tumour conversion to an immunological hot state. Here, we report the upstream and ligand of the RNA virus sensor pathway functions in irradiated cancer tissues. all: The RIG-1 mediated virus sensing pathway is found to play a role in radiotherapy induced cellular immune reactions.
- Subjects
GENE expression; DENDRITIC cells; IMMUNE response; CANCER cells; CELL lines
- Publication
Communications Biology, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-023-05080-x