跳转元件通过RIG-I介导的病毒感知途径增强了放射治疗诱导的细胞免疫反应。
Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways.
发表日期：2023 Aug 05
作者：
Junyan Du, Shun-Ichiro Kageyama, Riu Yamashita, Kosuke Tanaka, Masayuki Okumura, Atsushi Motegi, Hidehiro Hojo, Masaki Nakamura, Hidenari Hirata, Hironori Sunakawa, Daisuke Kotani, Tomonori Yano, Takashi Kojima, Yamato Hamaya, Motohiro Kojima, Yuka Nakamura, Ayako Suzuki, Yutaka Suzuki, Katsuya Tsuchihara, Tetsuo Akimoto
来源：
Cellular & Molecular Immunology
摘要：
放射治疗(RT)加免疫治疗是一种有前景的方法，然而，治疗效果不够，分子机制需要澄清以进一步开发联合疗法。在这里，我们发现RNA病毒感受器途径在非小细胞肺癌(NSCLC)和食管鳞癌(ESCC)细胞系中主导调控细胞免疫应答。值得注意的是，转座元件(TEs)，特别是长端重复序列(LTRs)，作为RNA病毒感受器RIG-I的关键配体，通过mTOR-LTR-RIG-I轴诱导细胞免疫应答以及树突状细胞和巨噬细胞的浸润。此外，在食管鳞癌患者组织中观察到RIG-I依赖的免疫激活。单细胞RNA测序和空间转录组分析揭示了放射治疗诱导LTRs在免疫和癌细胞中的表达以及RNA病毒感受器途径；同时发现该途径介导肿瘤转化为免疫高温状态。在这里，我们报道了RNA病毒感受器途径在受放疗癌组织中的上游和配体功能。© 2023. Springer Nature Limited.
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.© 2023. Springer Nature Limited.