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Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways

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 resp...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404237/
https://www.ncbi.nlm.nih.gov/pubmed/37543704
http://dx.doi.org/10.1038/s42003-023-05080-x
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author 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
author_facet 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
author_sort Du, Junyan
collection PubMed
description 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.
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spelling pubmed-104042372023-08-07 Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways 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 Commun Biol Article 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. Nature Publishing Group UK 2023-08-05 /pmc/articles/PMC10404237/ /pubmed/37543704 http://dx.doi.org/10.1038/s42003-023-05080-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title_full Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title_fullStr Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title_full_unstemmed Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title_short Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways
title_sort transposable elements potentiate radiotherapy-induced cellular immune reactions via rig-i-mediated virus-sensing pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10404237/
https://www.ncbi.nlm.nih.gov/pubmed/37543704
http://dx.doi.org/10.1038/s42003-023-05080-x
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